*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH (Brighton, Ann Arbor, Canton, Chelsea), Livonia, Genesys, Hurley, LVHN

Eligibility Criteria:

Eligibility Criteria for Preregistration to Step 0

3.1.1 Patient must be ≥ 18 and ≤ 75 years of age.

3.1.2 Patient must have an ECOG performance status between 0-3

3.1.3 Patient must be newly diagnosed with B-ALL or is suspected to have ALL

3.1.4 Patient must not have a diagnosis of BCR/ABL T-ALL.

3.1.5 Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden prior to study registration to Step 1 are eligible.

3.1.6 Patients who started any kind of TKI prior to study registration to Step 1 are allowed to proceed on the study if they received no more than 14 days of TKI.

3.1.7 Patient must not have unstable epilepsy that requires treatment.

3.1.8 Patients with lymphoid blast crisis CML are not eligible 

Eligibility Criteria for Registration to Step 1

3.2.1 Patient must have a diagnosis of Ph+ ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center.

3.2.2 Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. 

***PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELGIBILITY LIST***

**ePRO training required prior to first patient enrollment.**

Ages Eligible for Study:	18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Eligibility Criteria:

Step 0 Preregistration

3.1.1 Patient must be = 18 years of age.

3.1.2 Patient must have the ability to understand and the willingness to sign an informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be eligible.

3.1.3 Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if secondary to pain).

3.1.4 Patient must have newly diagnosed multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria.

3.1.5 Patients must be considered ineligible for autologous stem cell transplantation by the treating physician, or willing to delay stem cell transplantion until first relapse or later.

NOTE: Stem cell collection is allowed on study.

3.1.6 Patient must agree to register to the mandatory RevREMS program and be willing and able to comply with the requirements of RevREMS. See Section 8 for details.

3.1.7 Patient must not have any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products.

3.1.8 Patient must be able to undergo diagnostic bone marrow aspirate following preregistration.

NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies for clonoSEQ® Assay.

NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from the Clonality (ID) test within fourteen (14) days of receipt and reconciliation of fresh bone marrow specimen to the submitting institution.

Eligibility Criteria- Step 1 Registration

3.2.1 Patient must meet all eligibility criteria in Section 3.1 with exception of Section 3.1.5.

3.2.2 Institution must have received the Clonality (ID) test results from Adaptive Biotechnologies and dominant sequences must have been identified.

3.2.3 Patient must have standard risk MM as defined by the Revised International Staging System (RISS) Stage I or II.31

NOTE: R-ISS Stage is based on serum ß2 microglobulin, albumin and LDH levels along with presence of chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH). Presence of del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these, including any other findings, are standard risk.

R-ISS Stage

Stage I: ISS Stage I [ß2 microglobulin<3.5 mg/L, albumin>3.5 g/dL] AND standard-risk CA AND normal LDH

Stage II: Not R-ISS Stage I or III

Stage III: ISS Stage III [ß2 microglobulin>5.5 mg/L] AND high-risk CA OR high LDH (>upper limit of normal) [patients with Stage III are ineligible]

3.2.4 Patient must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to registration:

• = 1g/dL monoclonal protein (M-protein) on serum protein electrophoresis
• = 200 mg/24 hours of monoclonal protein on a 24-hour urine protein electrophoresis
• Involved free light chain = 10 mg/dL or = 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
• Monoclonal bone marrow plasmacytosis = 30% (evaluable disease)

3.2.5 Patients must have a SPEP UPEP, and serum FLC assay performed within 28 days prior to registration. In addition, a bone marrow biopsy and/or aspirate is required within 28 days if bone marrow is being followed for response.

NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine. Measurable disease in the serum is defined as having a serum M-spike = 1 g/dL. Measurable disease in the urine is defined as having a urine M-spike = 200mg/24 hr.

3.2.6 Patient must have adequate organ and marrow function as defined below (these must be obtained = 14 days prior to Step 1 registration)

- Calculated creatinine clearance >30 mL/min

- Absolute neutrophil count (ANC) =1000/mm3

- Untransfused Platelet count =75,000/mm3

- Hemoglobin =8.0 g/dL

- Total bilirubin = 1.5 x ULN (Institutional upper limit of normal)

- ALT and AST = 3 x ULN

3.2.7 Patient must have received no more than one cycle (28 days or less) of prior chemotherapy and no more than 160mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to symptomatic lesions is allowed provided there are no residual toxicity related to radiation and blood counts meet the study requirements. Radiation treatment must be completed at least 14 days prior to Step 1 registration.

3.2.8 Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

All females of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 1 registration to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment.

Please see Appendix V: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal

(amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

3.2.9 Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception [for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment] OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).

Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception] OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy.

Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.

3.2.10 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.

3.2.11 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

3.2.12 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.

3.2.13 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.

3.2.14 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. Patients must not have evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within 6 months prior to Step 1 registration.

3.2.15 Patient must not have peripheral neuropathy = Grade 2 on clinical examination or grade 1 with pain at time of Step 1 registration.

3.2.16 Patient must not have any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.

3.2.17 Patient may have a history of current or previous deep vein thrombosis (DVT) or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.

3.2.18 Patients with a history of chronic obstructive pulmonary disease (COPD) must have FEV1 testing done within 28 days prior to Step 1 registration and the forced expiratory volume in 1 second (FEV1) must be > 50% of predicted normal.

3.2.19 Patient must not have moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.

NOTE: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to register.

3.2.20 Patient must not receive any other concurrent chemotherapy, or any ancillary therapy considered investigational while on this protocol.

NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.

Eligibility Criteria- Step 2 Randomization

3.3.1 Institution must have received Tracking (MRD) test results from Adaptive Biotechnologies.

3.3.2 Patient must have completed the Step 1 Induction phase of this protocol without experiencing progression.

3.3.3 Patient must be registered to Step 2 within 8 weeks of completing Step 1 Induction Treatment, counting from last day of completion of last cycle.

3.3.4 Patient must not have received any non-protocol therapy outside of the assigned Step 1 Induction treatment including stem cell transplant.

3.3.5 Patient must have an ECOG performance status (PS) of 0-2. (PS 3 allowed if secondary to pain).

3.3.6 Any adverse event(s) related to Step 1 Induction Treatment must have resolved to grade 2 or less.

3.3.7 Patient must have adequate organ and marrow functions as defined below (these must be obtained within 14 days prior to Step 2 randomization).

3.3.7.1 Hemoglobin = 8 g/dL.

3.3.7.2 Platelet count = 50,000/mm3.

3.3.7.3 Absolute neutrophil count (ANC) = 1000/mm3.

3.3.7.4 Calculated creatinine clearance = 30 mL/min.

3.3.7.5 Total bilirubin = 1.5 x ULN (Institutional upper limit of normal).

3.3.7.6 ALT and AST < 3 X ULN

3.3.8 Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

All females of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment.

Please see Appendix V: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche

at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Female of childbearing potential? ______ (Yes or No)

Date of blood test or urine study: ___________.

3.3.9 Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception [for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment] OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).

Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception] OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy.

Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.

Eligibility Criteria:

-Patients must have a life expectancy of at least 24 months
-ECOG PS 0-3
-Patients must have a newly diagnosed colon or rectal cancer within 60 days of registration and have not yet received radiation or chemotherapy.
-Patients must have Stage I, II, or III disease at the time of enrollment and will be treated with curative-intent.
-Patients are not eligible if they are already enrolled on a treatment clinical trial at the time of registration. They can remain on the study if they subsequently enroll on a treatment clinical trial during the study time period.
-Patients who choose to not receive radiation and/or chemotherapy after a curative-intent surgery are eligible to participate.

Complete Participant contact information sheet at consent. Form in CREDIT documents library

Eligibility Criteria:

3.3.1 Patient must be ≥ 18 years of age at the time of registration.

3.3.2 Patient must have been between the ages of 15-39 at the time of their first primary cancer diagnosis of Hodgkin Lymphoma or Non-Hodgkin lymphoma (NHL).

3.3.3 Patient must have completed therapy (with a complete response, per clinician determination) at the time of registration.

3.3.4 Patients last date of prior systemic therapy for first primary diagnosis for Hodgkin Lymphoma or Non-Hodgkin Lymphoma must have been within one year prior to registration.

NOTE: Systemic therapy refers to all anti-cancer therapy, including but not limited to chemotherapy, IV or oral targeted medications, or radiation, and administered via a clinical trial or standard approach.

3.3.5 Patient must have an ECOG Performance Status of 0-3.

3.3.6 Patient must be English speaking in order to be able to complete the required QOL forms on this study.

NOTE: Sites cannot translate the associated QOL forms.

3.3.7 Patient must not be receiving active therapy for Hodgkin Lymphoma or Non-Hodgkin Lymphoma.

3.3.8 Patient must have internet access through computer, tablet, or smartphone.

3.3.9 Patient must have email address.

3.3.10 Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible. 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELGIBILITY LIST** 

Eligibility Criteria

Patient Eligibility Criteria for Step 0 (OPEN Screening Registration)

-Patient must be ≥ 18 years of age.

- Patient must be fluent in written and spoken English OR Patient must be fluent in written and spoken Spanish

- Patient must present with new or established pathologically proven HR+ HER2- metastatic breast cancer at the time of Step 0.

- Patient must have initiated any of the CKD4/6 inhibitors (Palbociclib or Ibrance, Ribociclib or Kisqali, Abemaciclib or Verzenio) within 30 days prior to consenting to Step 0 or have received a prescription order with stated intent to initiate within 30 days following Step 0 consent.

NOTE: Patients who have been treated previously with anticancer treatments other than CDK4/6 inhibitors are eligible. NOTE: CDK4/6 inhibitors must be provided/supplied as a single agent blister pack. If the medication is supplied as capsules in a pill bottle (e.g., Ibrance capsules), patient is not eligible.

NOTE: Ribociclib (Kisgali) and Abemaciclib (Verzenio) are only available in blister packs. Palbociclib (Ibrance) is the only CDK4/6 inhibitor that might be available in a capsule formulation. However, this is an outdated formulation and is rarely prescribed as a new start. The format of ordered Palbociclib can be determined based on the prescription order.

- Patients must not have been previously treated with any of the following CDK4/6 inhibitors: Palbociclib or Ibrance, Ribociclib or Kisqali, and Abemaciclib or Verzenio.

- Patients must not already be enrolled in a therapeutic clinical trial that monitors CDK4/6 inhibitors.

- Patient must confirm that they intend to receive their care or monitoring at an NCORP site.

- Patient must have a personal mobile phone in which they are able and willing to send and receive text messages. 

NOTE: The restriction to those with mobile phone access with text messaging is based on the primary intention of the study which involves the use of text messaging to improve adherence.

- Patient must have an email address.

NOTE: The restriction to those with an email address is based on the primary intention of the study which involves patients responding to questions regarding their reasons for non-adherence after every missed dose to improve adherence.

- Patient must have the ability to understand and the willingness to sign a written informed consent document.

NOTE: Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available are not eligible.

- Patient must not have an ECOG Performance Status ≥ 3. OR Patient must not be deemed medically unable to participate in the study by the study investigators or an oncology clinician (i.e., referral to hospice).

- Patient must not be enrolled in other trials offering financial assistance.

NOTE: Gift cards for survey completion, parking passes, or free medication provided as part of therapeutic trials are not considered financial assistance.

Patient Eligibility Criteria for Step 1 (OPEN Randomization)

- Patient must meet all the eligibility criteria for Step 0 outlined in Section 3.2.1.

-Patient must have signed a written informed consent form.

- Patient must have completed Baseline Survey within 30 days of the date of Step 0 Registration.

- Patients must have initiated their CDK 4/6 inhibitors within 30 days of the date of Step 0 Registration. 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

BIOPSIES ARE NO LONGER PROVIDED BY STUDY FUNDS. PATIENTS MUST MATCH ON NON-STUDY FUNDED REPORTS TO BE ELIGIBLE

Step 0 Eligibility: **Check for eligibility to EAQ152 COMET Step 1**
Please note: it is estimated to take 6-8 weeks to be assigned to a treatment on this trial.
-Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma that has progressed following at least one line of standard systemic therapy and/or for whose disease no standard treatment exists that has been shown to prolong survival.
-Patients must have measurable disease.
-Patients must meet one of the following:
--have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling. Biopsy must not be considered to be more than minimal risk to the patient. OR
--will be undergoing a procedure due to medical necessity during which the tissue may be collected OR
--tissue blocks collected within 6 mo prior to pre-reg are available for a patient who has not received any intervening therapy that is considered to be targeted- the patient may have received cytoxic chemo for up to 4 cycles but must not have responded
-Patient must not require the use of full dose coumadin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted.
-Patients must have ECOG performance status 0- 1
-Any prior therapy, radiotherapy (except palliative radiation therapy of 30 Gy or less), or major surgery must have been completed greater than or equal to 4 weeks prior to treatment on MATCH and patient must be recovered from adverse events due to prior therapy (except alopecia and lymphopenia)
-Palliative radiation therapy must have been completed at least 2 weeks prior to enrollment on a MATCH treatment arm and patient must have recovered from any adverse events of this therapy.
-Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy greater than or equal to 4 weeks prior to registration.
-NOTE: patients may receive non-protocol treatment after biopsy until they receive notification of results as specified per protocol; however, patients will need to be off of therapy for at least 4 weeks before receiving MATCH treatment.
-Patients with brain mets or primary brain tumors must have completed tx, surgery or RT at least 4 weeks prior to tx.
-Patients must have discontinued steroids greater than or equal to 1 week prior to registration (see protocol for exceptions). Patients with glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for one week prior to registration
-No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval

Step 1 Eligibility:

-See the specific subprotocol eligibility
-Some patients may be eligible to have their results rerun in Matchbox, even if they did not match to a treatment initially. See protocol for details.

Step 2 Eligibility:
-Patient's disease has progressed on Step 1 treatment or could not tolerate assigned treatment.
-Patients must meet one of the following criteria:
--No response and progression occurred less than 6 months from start of Step 1 treatment AND the MATCH assay results (received during Step 0) indicated > 1 targeted treatment.
--Progression occurred after a (1) response OR (2) after greater than or equal to 6 months from start of Step 1 treatment. 
-Patients must meet eligibility criteria for biopsy

Patient can be registered to subsequent steps depending on eligibility for further subprotocols.

Subprotocol A eligibility (in addition to master eligibility):
-Patient’s tumor must have either:
--Activating mutations of EGFR (del 19, L858R) by MATCH NGS assay. OR
--Any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S EGFR L861Q, EGFR S768I OR
--EGFR T790M de novo or in combination with other mutations.
-Note: tumors with an exon 20 insertion alone without the above mutations will be excluded.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG
-Patients must have an ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a LVEF < LLN.
-Patients must have less than or equal to Grade 1 renal function defined:
--Creatinine less than or equal to 1.5 x normal institutional limits OR
--Measured Creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal or as calculated by the Cockcroft-Gault Equation.
-Patients must not have had prior treatment with an EGFR TKI (e.g. Afatinib, Erlotinib, Gefitinib, Neratinib, Dacomitinib, AZD9291, Cabertinib, CO-1696).
-Patients with non-small cell lung cancer and small cell lung cancer will be excluded.
-Patients with a history of interstitial lung disease will be excluded.
-Patients must have less than or equal to Grade 1 diarrhea at baseline. 

Subprotocol B Eligibility (in addition to master protocol):
-Patient’s tumor must have activating HER2 mutation as determined by the MATCH NGS
assay. These mutations include: D769Y, D769H, P780_Y781insGSP, L755S, V777L, V842I, L755_S760>A, A775_G776insYVMA, M774_A775insAYVM, E321G, G309A,                                                  •   S310F, G309E, S310Y
--Additionally, any inframe insertions in exon 20 will be considered an activating mutation
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment
assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG
-Patients must have an ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a LVEF < LLN. 
-Patients must have less than or equal to Grade 1 diarrhea at baseline
-Patients with a history of interstitial lung disease will be excluded.
-Patients must not have had prior treatment with any of the following TKIs, which have
known activity against HER2 kinase:Neratinib, Afatinib, AC-480 (BMS-599626), AEE 788, AST 1306, AZD8931, Canertinib (CI 1033), CP-724714, CUDC-101, Dacomitinib, Lapatinib, Perlitinib, TAK285
-Patients must have less than or equal to Grade 1 renal function defined:
--Creatinine less than or equal to 1.5 x normal institutional limits OR
--Measured Creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal or as calculated by the Cockcroft-Gault Equation.
-Patients with non-small cell lung cancer will be excluded.

Subprotocol C1 eligibility (in addition to Master eligibility):
-Patient must have MET amplification as defined by the MATCH NGS assay. Amplified MET will be defined as = 7 copies/cell.
-Patient must not have had any of the following prior therapies: AMG 337, BMS 777607, Cabozantinib (XL184), Crizotinib (PF02341066), EMD1214063, Foretinib (GSK1363089) (XL880), Golvatinib (E7050), IncB28060 (INC280), JNJ 8877605, MGCD265, MK2461, MSC2156119J, PF 04217903, SGX523, Tivantinib (ARQ197) or any other novel MET TKI with any MET inhibitory activity IC50 < 1 uM. Prior anti-HGF or anti-MET antibodies are acceptable.