Targeted Therapy for Cancer

Recruiting in Palo Alto (17 mi)

+1582 other locations

Overseen by Keith T Flaherty

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

Research Team

Keith T Flaherty

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with advanced solid tumors, lymphomas, or multiple myeloma that have worsened after standard treatment or lack a consensus treatment. Participants must be finished with previous treatments and recovered from their effects, not expect to conceive children, have an ECOG status of <=1 indicating they are relatively active, and meet specific health criteria including heart function and blood tests.

Inclusion Criteria

Patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration; patients that are pregnant or breast feeding are excluded

Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse prior to study entry, for the duration of study participation, and for 4 months after completion of study

It's been over 4 weeks since my last cancer treatment or major surgery, and any side effects are mild.

Exclusion Criteria

Patients living outside the US are excluded

I do not have any of the excluded medical conditions or treatments.

You have abnormal blood test results.

Treatment Details

Interventions

• Afatinib (Kinase Inhibitor)
• Binimetinib (Kinase Inhibitor)
• Capivasertib (Kinase Inhibitor)
• Copanlisib (Kinase Inhibitor)
• Dabrafenib (Kinase Inhibitor)
• Dabrafenib Mesylate (Kinase Inhibitor)
• Dasatinib (Kinase Inhibitor)
• Defactinib (Kinase Inhibitor)
• Defactinib Hydrochloride (Kinase Inhibitor)
• Erdafitinib (Kinase Inhibitor)
• FGFR Inhibitor AZD4547 (Kinase Inhibitor)
• Ipatasertib (Kinase Inhibitor)
• Larotrectinib (Kinase Inhibitor)
• Osimertinib (Kinase Inhibitor)
• PI3K-beta Inhibitor GSK2636771 (Kinase Inhibitor)
• Sapanisertib (Kinase Inhibitor)
• Taselisib (Kinase Inhibitor)
• Ulixertinib (Kinase Inhibitor)
• Vismodegib (Kinase Inhibitor)

Trial Overview The MATCH trial is testing whether targeting therapy based on genetic abnormalities in the tumor cells can benefit patients whose cancer has progressed. It involves genetic testing to identify mutations or changes in the tumor's DNA and then matching patients with therapies specifically designed to target those genetic features.

Participant Groups

Group I: Subprotocol Z1M (LAG-3 expression >= 1%) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1.Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation) Experimental Treatment 3 Interventions

Patients with a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration receive ulixertinib (BVD-523FB) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group III: Subprotocol Z1K (AKT mutation) Experimental Treatment 3 Interventions

Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group IV: Subprotocol Z1I (BRCA1 or BRCA2 gene mutation) Experimental Treatment 3 Interventions

Patients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group V: Subprotocol Z1H (PTEN mutation) Experimental Treatment 4 Interventions

Patients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group VI: Subprotocol Z1G (PTEN loss) Experimental Treatment 4 Interventions

Patients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group VII: Subprotocol Z1F (PIK3CA mutation) Experimental Treatment 7 Interventions

Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment as well as CT or MRI at baseline and repeated every 2 cycles for the first 26 cycles then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step.

Group VIII: Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion) Experimental Treatment 8 Interventions

Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib (LOXO-101) PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.

Group IX: Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC) Experimental Treatment 3 Interventions

Patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 30 minutes on days 1 and 15 for 4 cycles and then on day 1 every 28 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group X: Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein) Experimental Treatment 3 Interventions

Patients with CDK4 or CDK6 amplification and tumor Rb protein receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XI: Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC) Experimental Treatment 3 Interventions

Patients with CCND1, 2, or 3 amplification that have tumor Rb expression by IHC receive palbociclib PO QD for 21 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XII: Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61) Experimental Treatment 3 Interventions

Patients with NRAS mutation in codon 12, 13, or 61 receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XIII: Subprotocol Y (Akt mutation) Experimental Treatment 3 Interventions

Patients with Akt mutation receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XIV: Subprotocol X (DDR2 S768R, I638F, or L239R mutation) Experimental Treatment 3 Interventions

Patients with DDR2 S768R, I638F, or L239R mutation receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XV: Subprotocol W (FGFR pathway aberrations) Experimental Treatment 3 Interventions

Patients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XVI: Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation) Experimental Treatment 9 Interventions

Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Group XVII: Subprotocol U (NF2 inactivating mutation) Experimental Treatment 4 Interventions

Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XVIII: Subprotocol T (SMO or PTCH1 mutation) Experimental Treatment 9 Interventions

Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or nuclear study during screening, tumor biopsy on study and CT scan, MRI and blood sample collection throughout the study.

Group XIX: Subprotocol S2 (GNAQ or GNA11 mutation) Experimental Treatment 3 Interventions

Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XX: Subprotocol S1 (NF1 mutation) Experimental Treatment 3 Interventions

Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXI: Subprotocol R (BRAF fusion or BRAF non-V600 mutation) Experimental Treatment 3 Interventions

Patients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXII: Subprotocol Q (HER2 amplification) Experimental Treatment 4 Interventions

Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group XXIII: Subprotocol P (PTEN loss) Experimental Treatment 3 Interventions

Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXIV: Subprotocol N (PTEN mutation or deletion and PTEN expression) Experimental Treatment 3 Interventions

Patients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXV: Subprotocol M (TSC1 or TSC2 mutation) Experimental Treatment 3 Interventions

Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Group XXVI: Subprotocol L (mTOR mutation) Experimental Treatment 3 Interventions

Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Group XXVII: Subprotocol K2 (FGFR mutation or fusion) Experimental Treatment 7 Interventions

Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI, and tumor biopsy throughout the study.

Group XXVIII: Subprotocol K1 (FGFR amplification) Experimental Treatment 7 Interventions

Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.

Group XXIX: Subprotocol J (HER2 amplification >= 7 copy numbers) Experimental Treatment 9 Interventions

Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment.

Group XXX: Subprotocol I (PIK3CA mutation) Experimental Treatment 3 Interventions

Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXXI: Subprotocol H (BRAF V600E/R/K/D mutation) Experimental Treatment 5 Interventions

Patients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXXII: Subprotocol G (ROS1 translocation or inversion) Experimental Treatment 3 Interventions

Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXXIII: Subprotocol F (ALK translocation) Experimental Treatment 3 Interventions

Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXXIV: Subprotocol E (EGFR T790M or rare activating mutation) Experimental Treatment 8 Interventions

Patients with EGFR T790M or rare activating mutation receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment.

Group XXXV: Subprotocol C2 (MET exon 14 deletion/mutation) Experimental Treatment 6 Interventions

Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study.

Group XXXVI: Subprotocol C1 (MET amplification) Experimental Treatment 6 Interventions

Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation and collection of blood samples throughout the study. Patients may undergo biopsy at screening, on study, and/or at end of treatment.

Group XXXVII: Subprotocol B (HER2 activating mutation) Experimental Treatment 4 Interventions

Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group XXXVIII: Subprotocol A (EGFR activating mutation) Experimental Treatment 10 Interventions

Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Afatinib is already approved in Canada, Japan for the following indications:

Approved in Canada as Gilotrif for:

• Non-small cell lung cancer

Approved in Japan as Giotrif for:

• Non-small cell lung cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School