Inclusion Criteria:

• HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) according to current American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines. Central testing is not required * Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on pretreatment biopsy material). Hormone receptor positive status can be determined by either known positive estrogen receptor (ER) or known positive progesterone receptor (PR) status; hormone receptor negative status must be determined by both known negative ER and known negative PR
• Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0 tumors are not eligible at initial breast cancer diagnosis are not eligible)
• Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or lymph nodes per the surgical pathology report are eligible; however, patients with HR+ HER2+ cancers must have node-positive residual disease per the surgical pathology report in order to qualify for the study. The presence of residual invasive disease in the breast is not mandatory for these patients
• Patients with weakly ER-positive (1-10%) breast cancer (based on the pretreatment core biopsy) are eligible even if they have node-negative disease per the surgical pathology report
• The residual disease tissue (breast and/or lymph nodes) is not required to be HER2-positive, as eligibility for NCI-2020-03770 (A011801) is based on a positive HER2 status at the time of the initial breast cancer diagnosis * Note: The presence of micrometastases in lymph nodes after preoperative therapy counts as residual disease, whereas the presence of isolated tumor cells does not
• Patients with synchronous bilateral invasive disease are eligible provided both lesions were confirmed to be HER2-positive, and at least one of the lesions meets the criteria outlined above. Multifocal disease is allowed, as long as the largest biopsied breast tumor was HER2-positive
• Patients must have received neoadjuvant chemotherapy with one of the following regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin (TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P)); docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P)); fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FAC-TH(P)), or fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)). Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is acceptable
• Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.
• Prior treatment must have consisted of >= 6 cycles of chemotherapy and HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9 weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food and Drug Administration [FDA]-approved biosimilars). Patients who have received at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also eligible if they received >= 6 cycles of systemic therapy prior to enrollment. Note: Patients who complete at least nine of a planned twelve doses of weekly paclitaxel, or three of a planned four doses of docetaxel, but discontinue prematurely due to toxicity are eligible. Patients receiving dose-dense chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane) instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is also allowed.
• Patients who received neoadjuvant systemic therapy which included experimental HER2-targeted therapy/therapies are potentially eligible, as long as the investigational agent was not a HER2-targeted antibody-drug conjugate (e.g. T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
• Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These patients will be randomized to receive a further 14 cycles of T-DM1 and tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been administered =< 5 weeks prior to registration * Note: Both of the following two criteria need to be met for the patient to be eligible for this study
• An interval of no more than 12 weeks between the completion date of the last definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither given, breast surgical date) and the date of registration. Concurrent radiation therapy is permitted while receiving study treatment
• Patients must be registered on study within =< 180 days of the date of the most recent definitive breast cancer surgery (not including reconstructive surgery)
• All systemic chemotherapy should have been completed preoperatively unless participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design, drugs, and eligibility). However, patients who received 4 cycles of neoadjuvant THP off study can receive a further 2-4 cycles of chemotherapy postoperatively to meet eligibility for A011801. Patients who participated in EA1181 or MA41 and proceeded to surgery immediately after the de-escalated trial regimen must receive postoperative chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles post-operatively). The postoperative chemotherapy regimen prescribed is at the discretion of the treating oncologist (i.e. 2-4 cycles AC or THP, other). Continuation of trastuzumab + pertuzumab (HP) pre- or post-operatively as maintenance therapy (while awaiting a surgical date or an official pathology report) is allowed for all study participants
• Toxicities related to prior systemic treatment should have resolved or be at baseline, apart from alopecia and peripheral neuropathy =< grade 1
• Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as follows:
• Breast surgery: total mastectomy with no gross residual disease at the margin of resection, or breast-conserving surgery with histologically negative margins of excision
• For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection
• Lymph node surgery ** The axilla needs to be evaluated with either sentinel node biopsy or axillary lymph node dissection. If patients have a sentinel lymph node biopsy and sentinel nodes are negative, no further axillary treatment is necessary. If patients have isolated tumor cells (ITCs) in the setting of residual breast disease, at least one of the following is required: axillary lymph node dissection (ALND) or planned nodal irradiation. If patients have micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are required. Of note, co-enrollment on Alliance A011202 is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted to achieve eligibility)
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.0 x upper limit of normal (ULN) or direct bilirubin within the institutional normal range for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute percentage points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55% after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated once up to 3 weeks following the initial screening assessment to assess eligibility

Exclusion Criteria:

• No adjuvant treatment with any anti-cancer investigational drug within 28 days prior to registration
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to registration is required
• Patients with known active and/or untreated hepatitis B or hepatitis C or chronic liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has been treated and cleared and normal liver function are eligible to participate in the study if the other eligibility parameters are met
• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of registration
• Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the surgical pathology report
• Evidence of recurrent disease following preoperative therapy and surgery
• Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
• History of exposure to the following cumulative doses of anthracyclines: doxorubicin > 240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2. For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
• Cardiopulmonary dysfunction as defined by any of the following:
• History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria class >= II
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease
• High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular block (AV)-block (second degree AV-block type 2 [Mobitz 2] or third degree AV-block)
• Significant symptoms (grade >= 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy
• History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with prior trastuzumab treatment (e.g., during preoperative therapy)
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
• Current severe, uncontrolled systemic disease
• Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to registration or anticipation of the need for major surgery during the course of study treatment
• History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
• Peripheral neuropathy of any etiology that exceeds grade 1
• Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol
• Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to registration is prohibited.
• Please note that use of sensitive CYP3A substrates should be avoided two weeks before registration and during study treatment. Additionally, CYP3A4 or CYP2C8 inducers are prohibited as concomitant medications within 5 days following discontinuation of tucatinib treatment. Patients who require medications that are known to be sensitive substrates of CYP3A4 with a narrow therapeutic window should be excluded.

Inclusion Criteria:

• Patients must have histologically confirmed glioblastoma (IDH wild-type, MGMT promoter methylated) that has undergone resection or biopsy upon first recurrence. Recurrence at site of prior involvement is defined by histopathological evidence of viable neoplastic cells associated with any of the following: mitotic activity, increased proliferation rate, micro-endothelial proliferation, or pseudo-palisading necrosis
• Prior to resection or biopsy, patients must have measurable disease, defined as at least one bi-dimensional contrast-enhancing lesion with clearly defined margins, with 2 perpendicular diameters of at least 10 mm, visible on >= 2 axial slices
• Patients must have received first-line treatment of temozolomide plus radiotherapy
• Patients must not have received any prior therapy aside from resection or biopsy for their recurrent disease
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of selinexor (KPT-330) in combination with temozolomide in patients < 18 years of age, children are excluded from this study
• Karnofsky performance status >= 60% (Eastern Cooperative Oncology Group [ECOG] =< 2)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 10 g/dL
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/ alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 x institutional ULN
• Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retro-viral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• The effects of selinexor (KPT-330) and temozolomide on the developing human fetus are unknown. For this reason and because selective nuclear export inhibitors as well as deoxyribonucleic acid (DNA) alkylating agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 180 days after the last dose of temozolomide. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of study treatment administration
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

• Patients who have had chemotherapy must have full recovery of organ and marrow function following the nadir of the last chemotherapy cycle
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents
• Patients who have previously received bevacizumab
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor (KPT-330) or temozolomide
• History of hypersensitivity to dacarbazine (DTIC), since both dacarbazine and temozolomide are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC)
• Patients with uncontrolled intercurrent illness
• Pregnant women are excluded from this study because selinexor (KPT-330) is a selective inhibitor of nuclear export with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selinexor (KPT-330), breastfeeding is not allowed for mothers during treatment with selinexor (KPT-330) and for 7 days after the last dose. These potential risks may also apply to other agents used in this study
• Hospitalized patients with severe coronavirus disease of 2019 (COVID-19) who are >= 75 years old, or with a high-risk COVID-GRAM score, or with lactate dehydrogenase (LDH) > 370 (U/L) AND D-Dimer > 600 mcg/L FEU should not receive low-dose selinexor (KPT-330) pending additional results

Inclusion Criteria:

• Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-small cell lung cancer (NSCLC) that is not amenable to curative therapy including surgical resection or chemoradiation. Additional Cohort specific disease requirements include: Cohorts 1, 3, 3b, 5, 6 and 7: epidermal growth factor receptor (EGFR) exon 19 deletion (Exon19del) or Exon 21 L858R mutation; Cohort 2: EGFR Exon 20ins mutation. Cohorts 1,5,and6: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohort 2: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohorts 3and3b: Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second-line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Cohort 4: Participants need to currently be on an amivantamab IV Q2W regimen (1,050 mg or 1,400 mg depending on weight) for at least 8 weeks, as part of standard of care, an expanded access program, or as a rollover from a long-term extension, without any amivantamab dose reduction. Cohort 7: Participants must have progressed on or after the combination of amivantamab and lazertinib as the most recent line of treatment. The combination of amivantamab and lazertinib must have been administered as the first-line treatment for locally advanced or metastatic disease. Cohort 2, 3, 3b, and 7 only: Squamous NSCLC are excluded. EGFR mutation must have been identified as determined by Food and Drug Administration (FDA) approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states [US]) or an accredited local laboratory (sites outside of the US). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor
• All cohorts except Cohort 4: Participants must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed If only 1 non-irradiated measurable lesion exists, which undergoes a biopsy and is acceptable as a target lesion, the baseline tumor assessment scans should be performed at least 14 days after the biopsy
• May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
• Have adequate organ (renal, hepatic, hematological, coagulation and cardiac) functions
• Participant must have eastern cooperative oncology group (ECOG) status of 0 or 1
• Cohort 6: Must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months of study treatment
• A participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility

Exclusion Criteria:

• Participant has a medical history of interstitial lung disease (ILD), including drug induced ILD or radiation pneumonitis
• Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort
• Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary
• For all cohorts (with regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent Cytochrome (CYP3A4/5) inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1
• Other clinically active liver disease of infectious origin
• Participant has a history of clinically significant cardiovascular disease including, but not limited to: a) All cohorts: diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary; b) All cohorts (with regimens potentially including lazertinib): Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden); c) All cohorts (with regimens potentially including lazertinib): Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines; d) prolonged corrected QT interval by Fridericia (QTcF) interval greater than (>) 480 milliseconds (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate); e) uncontrolled (persistent) hypertension: systolic blood pressure >160 millimeter(s) of mercury (mmHg); diastolic blood pressure >100 mmHg; f) Congestive heart failure defined as NYHA class III-IV or hospitalization for congestive heart failure (CHF) (any New York Heart Association [NYHA] class) within 6 months of treatment initiation at Cycle 1/day 1 (C1D1); g) pericarditis/clinically significant pericardial effusion; h) myocarditis; i) baseline left ventricular ejection fraction (LVEF) below the institution's lower limit of normal at screening, as assessed by echocardiogram or multigated acquisition (MUGA) scan
• Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (less than or equal to [<=] 10 milligrams per day [mg/day] prednisone or equivalent) for at least 2 weeks prior to treatment allocation

KEY Inclusion Criteria:

1. Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL, for whom next available standard of care therapy is not available or deemed ineligible according to the investigator (Part 1A only) 2. Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 4. Life expectancy ≥ 12 months 5. International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only; 6. Adequate hematologic and organ function, as defined in the protocol.

KEY Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology 2. Another active malignancy, significant active disease or medical condition, as described in the protocol 3. Peripheral neuropathy Grade ≥3 4. Treatment with any systemic anti-lymphoma therapy, except for participants with relapsed/refractory (R/R) DLBCL and participants with DLBCL transformed from an indolent follicular lymphoma after treatment with systemic anti-lymphoma therapy. 5. Any other therapy or investigational treatment within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment 6. Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol 7. Allergy/hypersensitivity to study drugs, as described in the protocol 8. Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol.Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Inclusion Criteria:

• Documented radiographic and histopathologic confirmed primary localized invasive breast cancer.
• Histologically documented TNBC (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/human epidermal growth factor 2 negative [HER2-]) defined as ER-negative and PR-negative (≤5% positive cells stain by IHC for both ER and PR), and negative HER2eu- status, confirmed on tumor sample.
• HER2eu negative will be defined as one of the following criteria:
• IHC 0 or 1+
• Single-probe average HER2 gene copy number of <6 signalsucleus
• Dual-probe fluorescent in-situ hybridization (FISH) HER2eu chromosome 17 (CEP17) non-amplified ratio of <2
• Globo H IHC H-score ≥15 from the residual primary site/or lymph node (if primary site is not available) tumor obtained at time of definitive surgery. Globo H expression will be determined during pre-screening by Central lab. Instructions for submission of slides/tumor tissue blocks are provided in the protocol and study Lab Manual.
• No evidence of metastatic disease in chest, abdomen and pelvis by CT or other adequate imagining during the Screening Phase. Imaging within 3 months prior to randomization is acceptable as baseline scan. Bone scans and imaging of the brain at screening is optional, and should be symptom directed.
• High risk patients with no evidence of disease after completing standard treatment and meeting ONE of the following criteria:
• Neoadjuvant chemotherapy followed by definitive surgery: Residual invasive disease following neoadjuvant chemotherapy defined as: A contiguous focus of residual invasive cancer in the surgical breast measuring ≥1 cm in diameter and/or with residual invasive cancer in at least one axillary node (micrometastases or macrometastases), as determined by local pathology review.
• Definitive surgery followed by adjuvant chemotherapy: Pathological Stage IIB, Stage IIIA , Stage IIIB, or Stage IIIC disease according to the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual.
• Must have completed a standard taxane, and/or anthracycline-based multi-agent chemotherapy regimen either in the neoadjuvant or adjuvant setting (e.g., National Comprehensive Cancer Network recommended regimens):.
• At least 4 cycles of a standard multi-agent chemotherapy regimen must have been received, unless precluded by toxicities
• Post operative adjuvant capecitabine or a platinum monotherapy in patients with residual disease after neoadjuvant chemotherapy is allowed.
• Randomization must occur within 12 weeks after completion of standard of care treatment (surgery and/or chemotherapy) and within 46 weeks from the date of definitive surgery. Note: patients receiving adjuvant capecitabine or platinum monotherapy after neoadjuvant multi-agent chemotherapy may be randomized and initiate study treatment during (or within 12 weeks after completion of) the adjuvant capecitabine or platinum monotherapy.
• All treatment-related toxicities resolved to Grade <1 on National cancer institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0) criteria (except hair loss and ≤Grade 2 neuropathy, which are acceptable).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Females must be either of non-childbearing potential, i.e., surgically sterilized (have documented sterilization, bilateral oophorectomy/salpingectomy at least 3 months before the start of the trial and/or hysterectomy), or one year postmenopausal; or if of childbearing potential must have a negative pregnancy test (urine or serum) at randomization.
• Males and females of childbearing potential and their partners must be willing to use effective contraception during the entire Treatment Phase period and for at least 4 weeks (28 days) after the last dose of study treatment.
• Adequate hematological, hepatic and renal function as defined below:
• Absolute neutrophil count (ANC) ≥1,500/µL
• Platelets ≥75,000/µL
• Hemoglobin ≥8.5g/dL
• Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥55 mL/min for subjects with creatinine levels >1.5 × institutional ULN (glomerular filtration rate can also be used in place of creatinine or creatinine clearance may be calculated per institutional standard)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
• Alkaline Phosphatase (ALP) ≤2.5 × ULN
• Serum total bilirubin ≤1.5 × ULN (unless Gilbert's disease is documented)
• Consent to participate with a signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved patient informed consent for the study prior to beginning any specific study procedures.
• Ability to understand and willingness to complete all protocol required procedures.

Exclusion Criteria:

• Local recurrence of or previous history of ipsilateral or contralateral invasive breast cancer within 10 years prior to randomization.
• Definitive clinical or radiologic evidence of metastatic disease
• Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.
• Have received any post-operative immunotherapy with antigen, antibody, immune checkpoint inhibitors (Programmed cell death-1 [PD-1]/ Programmed cell death-ligand-1inhibitors [PD-L-1], anti-cytotoxic T lymphocyte associated protein 4 [CTLA 4] therapy), or other anti-cancer vaccines (neoadjuvant receipt of immune checkpoint inhibitors will not be exclusionary if the patient meets all other eligibility criteria).
• Concomitant treatment with approved anticancer therapy or immunotherapy including checkpoint inhibitors (e.g. PD-1 inhibitors) or other investigational therapy, if expected during the study. Adjuvant capecitabine or platinum monotherapy is allowed during the study.
• A history of other malignancies (except non melanoma skin carcinoma, carcinoma in situ of the uterine cervix, follicular or papillary thyroid cancer) within 5 years prior to randomization.
• Have any active autoimmune disease or disorder that requires systemic immunosuppressive/immunomodulatory therapy. NOTE: Autoimmune diseases that are confined to the skin (e.g., psoriasis) that can be treated with topical steroids alone are allowed during the study.
• Oral/parenteral corticosteroid treatment (>5 mg/day of prednisone/equivalent), within 2 weeks prior to randomization or anytime during the study. NOTE: inhaled steroids for treatment of asthma; and topical steroids are allowed during the study.
• Any known uncontrolled concurrent illness that would limit compliance with study requirements, including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric disorders, or substance abuse.
• Any known hypersensitivity to active/inactive ingredients in the study drug formulation or known severe allergy or anaphylaxis to fusion proteins.
• Prior receipt of a glycoconjugate vaccine for cancer immunotherapy.
• Known history or positive for human immunodeficiency virus (HIV positive), unless on effective anti-retroviral therapy with undetectable viral load within 6 months of therapy (note: HIV testing not required for study entry).
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to randomization. Patients who have completed curative therapy for HCV are eligible. For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy. (note: HBV/HCV testing is not required for study entry).
• Any condition, including significant diseases and/or laboratory abnormalities that would place the patient at unacceptable risk for study participation.
• Currently pregnant or breastfeeding women.
• Currently participating in or has participated in a breast cancer therapeutic clinical trial within 4 weeks (24 days) prior to randomization.

Inclusion Criteria:

• Eight years or older with HNC diagnosis confirmed histologically o Stage 1-3 HNC pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, larynx, hypopharynx, nasopharyngeal, or oral cavity
• Plan to receive radiotherapy (>60 Gy), chemo-irradiation or bio-radiation either as primary or as a post-operative treatment to the head and neck region
• Eastern Cooperative Oncology Group Performance Status (ECOGPS) performance status 0 or 1
• Comply with the study protocol
• Capable of signing a written informed consent

Exclusion Criteria:

• An allergy, intolerance, or contraindication to colchicine
• Current treatment with colchicine for medical conditions, e.g. gout and Familial Mediterranean Fever (FMF)
• Estimated glomerular filtration rate (GFR) < 55 ml/min since colchicine should not be given
• Severe liver disease or current aminotransferase levels of more than 1.5 times the upper limit of the normal range
• Previous irradiation to the head and/or neck region
• Distant metastatic disease or locally recurrent disease
• Pre-existing skin rashes, ulcerations, or open wounds in the treatment area
• Known allergic and other systemic skin diseases even when not directly affecting irradiated fields
• Substance abuse, medical conditions, and/or social issues that would limit conduct or follow-up in the research study, in the opinion of the investigator
• Any condition that is unstable or could affect the safety of the patient and their compliance in the study as judged by the investigator
• Using high doses of non-steroidal anti-inflammatory drugs
• Pregnant and lactating women
• Psychiatric illness that would prevent the patient from giving informed consent
• Taking cetuximab or other radiosensitizing agents.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate diagnosed within the last 9 months. Patients on active surveillance with evidence of disease progression are eligible to the protocol as long as they meet the eligibility criteria and have a recent prostate biopsy (within 9 months)
• Low-risk and intermediate-risk patients are eligible according to the following guidelines:
• Low and intermediate-risk disease defined as:
• Clinical stage T1-T2 and Gleason =< 7 and prostate specific antigen (PSA) < 15 ng/ml
• Lymph node evaluation by either computed tomography (CT) or magnetic resonance imaging (MRI) and bone scan are optional and are left at the discretion of the treating physician
• Prostate MRI is recommended by not mandatory
• No alpha reductase inhibitors use within 2 weeks of randomization. A washout period of 2 weeks is required prior to randomization
• Eastern Cooperative Oncology Group status 0-1
• Judged to be medically fit for brachytherapy by a radiation oncologist
• Concurrent, neoadjuvant and/or adjuvant androgen deprivation therapy (ADT) is not permitted
• Prostate volume by trans-rectal ultrasound (TRUS) =< 60 cc
• International Prognostic Scoring System (IPSS) =< 20 (alpha blockers allowed)
• Patients must sign a study specific informed consent form prior to study entry
• Patients must by accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating center. Investigators must assure themselves that patients enrolled in this trial will be available for complete documentation of the treatment, adverse events, and follow up
• Protocol treatment is to begin within 4 weeks of patient randomization

Exclusion Criteria:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, or other solid tumors curatively treated with no evidence of disease for >= 5 years
• Prior or current bleeding diathesis
• Radical surgery for carcinoma of the prostate, prior pelvic radiation, prior chemotherapy for prostate cancer, prior transurethral resection of the prostate (TURP), prior cryosurgery of the prostate
• Stage T3b and evidence of nodal or distant metastatic disease on diagnostic CT, MRI or bone scan
• Subjects who have plans to receive other concomitant or post treatment adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as part of the treatment of prostate cancer
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial for fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulations defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immumo-compromised patients
• Patients with history of inflammatory colitis (including Crohn's disease and ulcerative colitis) or collagen vascular diseases including rheumatoid arthritis and lupus are not eligible
• Subjects who have a history of significant psychiatric illness
• Men of reproductive potential who do not agree that they or their partner will use an effective contraceptive method such as condom/diaphragm and spermicidal foam, intrauterine device (IUD), or prescription birth control pills

Inclusion Criteria:

• Age >= 18 years.
• HCC diagnosis confirmed by histology/cytology or clinically by American Association for Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Locally advanced, metastatic, or unresectable disease.
• Child Pugh class A.
• Barcelona clinic liver cancer (BCLC) stage B (not amenable to liver directed therapy) or stage C.
• Prior treatment with atezolizumab and bevacizumab combination with radiographic progression that necessitates change in treatment per treating physician. Patients with rapid progression on atezolizumab and bevacizumab (defined as patients who progressed radiographically in the first restaging scan that necessitates change in treatment) are excluded.
• Washout period >= 4 weeks prior to registration is required since last atezolizumab and bevacizumab dose.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. (Form is available on the Academic and Community Cancer Research United [ACCRU] website).
• Absolute neutrophil count (ANC) >= 1000/mm ^ 3 (obtained =< 28 days prior to registration).
• Platelet count >= 60,000/mm^3 (obtained =< 28 days prior to registration).
• Hemoglobin >= 8.5 g/dL (obtained =< 28 days prior to registration).
• Total bilirubin =< 3 x upper limit of normal (ULN) (obtained =< 28 days prior to registration).
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 5 x ULN (obtained =< 28 days prior to registration).
• International normalized ratio (INR) =< 2.3 or Prothrombin time (PT) =< 6 seconds above control OR if patient is receiving anticoagulant therapy and INR is within target range of therapy creatinine =< 1.5x ULN (obtained =< 28 days prior to registration).
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only.
• Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide informed written consent =< 28 days prior to registration.
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
• Note: During the active monitoring phase of a study (i.e., active treatment), participants must be willing to return to the consenting institution for follow-up.
• Willing to provide mandatory tissue specimens and blood specimens for correlative research purposes.

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception.
• Major surgery =< 4 weeks prior to registration.
• Liver directed therapy (transarterial chemoembolization [TACE], Y-90, liver directed radiation) =< 28 days prior to registration. Prior liver directed therapy > 28 days prior to registration is allowed as long as patient has at least one measurable untreated lesion by RECIST v1.1.
• Patients with rapid progression on atezolizumab and bevacizumab (who progressed radiographically in the first restaging scan that necessitates change in treatment) are excluded.
• Prior treatment =< 4 weeks prior to registration with anti-CTLA-4 antibody for HCC.
• Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.
• Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection excluding hepatitis C virus (HCV)
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Unstable cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients with chronic HBV infection as evidenced by detectable HBV surface antigen or HBV deoxyribonucleic acid (DNA) are eligible if on antiviral therapy and have HBV DNA < 100 IU/mL. Patients with active or resolved hepatitis C (HCV) infection as evidenced by detectable HCV ribonucleic acid (RNA) or antibody are eligible.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 4 weeks prior to registration.
• Other active malignancy =< 2 years prior to registration. Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• History of leptomeningeal carcinomatosis.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Current or prior use of immunosuppressive medication =< 14 days prior to registration. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
• Receipt of live attenuated vaccine =< 30 days prior to registration; Note: Patients, if enrolled, should not receive live vaccine whilst on study treatment and up to 30 days after the last dose of study treatment.
• Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• History of grade 3 or 4 immunotherapy related toxicity NCI CTCAE v5.0 due to prior regimen attributed to atezolizumab.

Inclusion Criteria:

• Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent, chemotherapy (chemo)-naive, HER2-positive endometrial serous carcinoma or endometrial carcinosarcoma
• Histologic confirmation of the original primary tumor is required. Submission of surgical pathology report (or endometrial biopsy pathology report in patients who never undergo hysterectomy) is required
• Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients who never undergo hysterectomy) at the time of study registration
• Patients may have measurable disease, non-measurable disease, or no measurable disease. In patients with measurable disease, lesions will be defined and monitored by RECIST v 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• For patients with uterine-confined (stage I) disease, the tumor must be invasive into the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined to a polyp will be excluded
• All patients must have tumors that are HER2 positive as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf. In general HER2 positivity is defined as any of the following:
• 3+ immunohistochemistry (IHC),
• 2+ IHC with positive in situ hybridization (ISH)
• Average HER2 copy number >= 6.0 signals/cell
• Average HER2 copy number >= 4.0 and < 6.0 signals/cell, with concurrent IHC 3+
• HER2/CEP17 ratio >= 4.0 signals/cell
• HER2/CEP 17 ratio >= 2.0 and < 4.0, with concurrent IHC 3+ IHC and ISH testing will be done locally, at each participating institution and interpreted by local pathologists. Alternatively, patients could be eligible if next generation sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be performed through any designated labs as per the National Cancer Institute (NCI) MATCH/NCI Combo-MATCH trial (https://ecog-acrin.orgci-match-eay131-designated-labs).Pathology report showing results of institutional HER2 testing (or NGS testing results)must be submitted.Sites must submit all results available (IHC, ISH, and NGS)
• Additionally, patients must have the following histologic types to be eligible:
• Serous adenocarcinoma (may include =< 10% non-serous histology)
• Carcinosarcoma with serous epithelial component (only the serous component needs to be HER2 positive; may include =< 10% non-serous histology)
• In cases where determination of serous is equivocal or challenging, aberrant p53 immunohistochemistry (IHC) (defined as overexpression of p53 compared to internal controls) will be sufficient for inclusion
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Age >= 18
• Platelets >= 100,000/mcl (within 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated Glomerular filtration rate (eGFR) >= 50 mL/min using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR). (within 14 days prior to registration)
• Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
• Although the uterus will have been removed in the vast majority of patients, for patients of child-bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Patients will be considered of non-reproductive potential if they are either:
• Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
• Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to registration
• Have a congenital or acquired condition that prevents childbearing
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

• Prior Therapy:
• Patients must NOT have received prior chemotherapy, biologic therapy, or targeted therapy for treatment of endometrial carcinoma
• Patients must NOT have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation includes external beam pelvic radiation therapy, external beam extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy
• NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted during study treatment. Planned use of vaginal brachytherapy must be declared at time of registration
• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to registration
• Patients may not have a planned interval cytoreduction or hysterectomy, prior to documentation of progression, after study registration
• Patients may not have planned external beam radiotherapy, prior to documentation of progression, after study registration
• Significant cardiovascular disease including:
• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg despite antihypertensive medications
• Myocardial infarction or unstable angina within 6 months prior to registration
• New York Heart Association functional classification II, III or IV
• Serious cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial fibrillation with controlled ventricular rate
• Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), uncontrolled interstitial lung disease, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
• Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to registration
• Women who are unwilling to discontinue nursing

Inclusion Criteria:

• A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
• The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• Female patients must be greater than or equal to 18 years of age.
• Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
• Age 50 years or under with spontaneous menses within 12 months; or
• Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
• Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
• Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
• The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
• Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• Patients may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
• For patients who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS (ductal carcinoma in situ) with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS (lobular carcinoma in situ) are eligible without additional resection.)
• For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
• Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
• By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
• By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
• Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
• Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
• Oncotype DX RS (recurrence score) requirements*:
• If node-negative:
• Oncotype DX RS must be RS 21-25, or
• Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as: low histologic grade with primary tumor size greater than 3 cm, intermediate histologic grade with primary tumor size greater than 2 cm, or high histologic grade with primary tumor size greater than 1 cm.
• If 1-3 nodes involved:
• Oncotype DX RS must be less than 26. * Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes the activity of certain genes in early-stage breast cancer) result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
• The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results. Patients with greater than or equal to 1% ER and/or PgR staining by IHC will be classified as positive.
• The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines based on local testing results.
• The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
• Short course of endocrine therapy of less than 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
• Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. This would include prior cancers treated with curative intent.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Radiation therapy should be used according to standard guidelines; the intended radiation therapy should be declared prior to pre-entry.

Exclusion Criteria:

• • Definitive clinical or radiologic evidence of metastatic disease.
• pT4 (pathological state) tumors, including inflammatory breast cancer.
• History of ipsilateral or contralateral invasive breast cancer. (Patients with synchronous and/or previous DCIS or LCIS are eligible.)
• If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation therapy), a mastectomy must have been performed for the current cancer.
• Life expectancy of less than 10 years due to co-morbid conditions in the opinion of the investigator.Known results from most recent lab studies obtained as part of routine care prior tostudy entry showing ANY of the following values:
• ANC (absolute neutrophil count) less than 1200/mm3;
• Platelet count less than 100,000/mm3;
• Hemoglobin less than 10 g/dL;
• Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than 1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin;
• AST(aspartate aminotransferase)(SGOT)/ALT (alanine transminase)(SGPT): greater than 3 × institutional ULN;
• Renal function of GFR (glomular filtration rate) less than 30 mL/min/1.73m2.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Any treatment with radiation therapy, chemotherapy, or biotherapy administered for the currently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen given for breast cancer prevention is allowed. Prior AI or GnRH for fertility preservation is allowed.
• Hormonally based contraceptive measures must be discontinued prior to pre-entry (including progestin/progesterone IUDs).
• Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible unless the HBV viral load is undetectable on suppressive therapy. Patients with a history of hepatitis C virus (HCV) infection are ineligible unless they have been treated and cured or have an undetectable HCV viral load if still on active therapy.
• Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to pre-entry.)
• Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.

Inclusion Criteria:

PRE-REGISTRATION:
• Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
• TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
• Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:
• No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
• Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
• No evidence of metastatic disease
• Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imagingREGISTRATION:
• Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
• Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
• No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
• Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Total Neuropathy Score < 2
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelet count >= 100,000/uL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =< 3.0)
• Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min (Calculated using the Cockcroft-Gault equation)
• No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
• No comorbid conditions that would prohibit curative-intent pancreatectomy
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
• Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration

Inclusion Criteria:

• Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses.
• Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of signing the informed consent. All genders are permitted.
• Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy.
• Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R mutation, and/or T790M.
• Documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy.
• Mandatory provision of FFPE tumour tissue.
• MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment.
• Measurable disease as defined by RECIST 1.1.
• Adequate haematological, liver, renal and cardiac functions, and coagulation parameters.
• ECOG performance status of 0 or 1.

Exclusion Criteria:

• Predominant squamous NSCLC, and small cell lung cancer.
• Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib.
• Prior or current treatment with savolitinib or another MET inhibitors.
• Spinal cord compression or brain metastases, unless asymptomatic and are stable.
• History or active leptomeningeal carcinomatosis.
• Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 and prior platinum-therapy related Grade 2 neuropathies with the exception of alopecia and haemoglobin ≥ 9.0 g/dL.
• Active/unstable cardiac diseases currently or within the last 6 months, clinically significant ECG abnormalities, and/or factors/medications that may affect QTc intervals.
• History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement.
• Known serious active infection including, but not limited to, tuberculosis, or HIV, HBV or HCV or gastrointestinal disease.
• Receipt of live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of study intervention.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required steroid treatment, or any evidence of clinically active ILD.
• Participants currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2.