Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

Conditions

• Advanced Lymphoma
• Advanced Malignant Solid Neoplasm
• Bladder Carcinoma
• Breast Carcinoma
• Cervical Carcinoma
• Colon Carcinoma
• Colorectal Carcinoma
• Endometrial Carcinoma
• Esophageal Carcinoma
• Exocrine Pancreas Carcinoma
• Gastric Carcinoma
• Glioma
• Head and Neck Carcinoma
• Hematopoietic and Lymphoid Cell Neoplasm
• Kidney Carcinoma
• Liver Carcinoma
• Lung Carcinoma
• Lymphoma
• Malignant Uterine Corpus Neoplasm
• Malignant Uterine Neoplasm
• Melanoma
• Multiple Myeloma
• Ovarian Carcinoma
• Prostate Carcinoma
• Rectal Carcinoma
• Recurrent Bladder Carcinoma
• Recurrent Breast Carcinoma
• Recurrent Cervical Carcinoma
• Recurrent Colon Carcinoma
• Recurrent Colorectal Carcinoma
• Recurrent Esophageal Carcinoma
• Recurrent Gastric Carcinoma
• Recurrent Glioma
• Recurrent Head and Neck Carcinoma
• Recurrent Liver Carcinoma
• Recurrent Lung Carcinoma
• Recurrent Lymphoma
• Recurrent Malignant Solid Neoplasm
• Recurrent Malignant Uterine Corpus Neoplasm
• Recurrent Melanoma
• Recurrent Multiple Myeloma
• Recurrent Ovarian Carcinoma
• Recurrent Pancreatic Carcinoma
• Recurrent Prostate Carcinoma
• Recurrent Rectal Carcinoma
• Recurrent Skin Carcinoma
• Recurrent Thyroid Gland Carcinoma
• Refractory Lymphoma
• Refractory Malignant Solid Neoplasm
• Refractory Multiple Myeloma
• Skin Carcinoma
• Thyroid Gland Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Adavosertib — DRUG
  Given PO
• Afatinib — DRUG
  Given PO
• Afatinib Dimaleate — DRUG
  Given PO
• Binimetinib — DRUG
  Given PO
• Biopsy Procedure — PROCEDURE
  Undergo tumor biopsy
• Biospecimen Collection — PROCEDURE
  Undergo collection of blood samples
• Capivasertib — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo computed tomography (CT)
• Copanlisib — DRUG
  Given IV
• Copanlisib Hydrochloride — DRUG
  Given IV
• Crizotinib — DRUG
  Given PO
• Cytology Specimen Collection Procedure — OTHER
  Optional correlative studies
• Dabrafenib — DRUG
  Given PO
• Dabrafenib Mesylate — DRUG
  Given PO
• Dasatinib — DRUG
  Given PO
• Defactinib — DRUG
  Given PO
• Defactinib Hydrochloride — DRUG
  Given PO
• Echocardiography Test — PROCEDURE
  Undergo echocardiography (ECHO)
• Erdafitinib — DRUG
  Given PO
• Fexagratinib — DRUG
  Given PO
• Ipatasertib — DRUG
  Given PO
• Laboratory Biomarker Analysis — OTHER
  Undergo molecular analysis
• Larotrectinib — DRUG
  Given PO
• Larotrectinib Sulfate — DRUG
  Given PO
• Magnetic Resonance Imaging — PROCEDURE
  Undergo magnetic resonance imaging (MRI)
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Nivolumab — BIOLOGICAL
  Given IV
• Osimertinib — DRUG
  Given PO
• Palbociclib — DRUG
  Given PO
• Pertuzumab — BIOLOGICAL
  Given IV
• PI3K-beta Inhibitor GSK2636771 — DRUG
  Given PO
• Radiologic Examination — PROCEDURE
  Undergo radiologic evaluation
• Radionuclide Imaging — PROCEDURE
  Undergo nuclear study
• Relatlimab — BIOLOGICAL
  Given IV
• Sapanisertib — DRUG
  Given PO
• Sunitinib Malate — DRUG
  Given PO
• Taselisib — DRUG
  Given PO
• Trametinib — DRUG
  Given PO
• Trastuzumab — BIOLOGICAL
  Given IV
• Trastuzumab Emtansine — BIOLOGICAL
  Given IV
• Ulixertinib — DRUG
  Give PO
• Vismodegib — DRUG
  Given PO

Study Details

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.

Key Dates

Start date

Aug 17, 2015

Status verified

Jan 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

6,452 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SCREENING

Arms

• Experimental: Subprotocol A (EGFR activating mutation)
  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.
• Experimental: Subprotocol B (HER2 activating mutation)
  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.
• Experimental: Subprotocol C1 (MET amplification)
  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.
• Experimental: Subprotocol C2 (MET exon 14 deletion/mutation)
  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.
• Experimental: Subprotocol E (EGFR T790M or rare activating mutation)
  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.
• Experimental: Subprotocol F (ALK translocation)
  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.
• Experimental: Subprotocol G (ROS1 translocation or inversion)
  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.
• Experimental: Subprotocol H (BRAF V600E/R/K/D mutation)
  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.
• Experimental: Subprotocol I (PIK3CA mutation)
  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.
• Experimental: Subprotocol J (HER2 amplification >= 7 copy numbers)
  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.
• Experimental: Subprotocol K1 (FGFR amplification)
  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.
• Experimental: Subprotocol K2 (FGFR mutation or fusion)
  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.
• Experimental: Subprotocol L (mTOR mutation)
  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.
• Experimental: Subprotocol M (TSC1 or TSC2 mutation)
  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.
• Experimental: Subprotocol N (PTEN mutation or deletion and PTEN expression)
  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.
• Experimental: Subprotocol P (PTEN loss)
  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.
• Experimental: Subprotocol Q (HER2 amplification)
  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.
• Experimental: Subprotocol R (BRAF fusion or BRAF non-V600 mutation)
  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.
• Experimental: Subprotocol S1 (NF1 mutation)
  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.
• Experimental: Subprotocol S2 (GNAQ or GNA11 mutation)
  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.
• Experimental: Subprotocol T (SMO or PTCH1 mutation)
  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.
• Experimental: Subprotocol U (NF2 inactivating mutation)
  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.
• Experimental: Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
  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.
• Experimental: Subprotocol W (FGFR pathway aberrations)
  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.
• Experimental: Subprotocol X (DDR2 S768R, I638F, or L239R mutation)
  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.
• Experimental: Subprotocol Y (Akt mutation)
  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.
• Experimental: Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
  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.
• Experimental: Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)
  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.
• Experimental: Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)
  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.
• Experimental: Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)
  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.
• Experimental: Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
  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.
• Experimental: Subprotocol Z1F (PIK3CA mutation)
  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.
• Experimental: Subprotocol Z1G (PTEN loss)
  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.
• Experimental: Subprotocol Z1H (PTEN mutation)
  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.
• Experimental: Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
  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.
• Experimental: Subprotocol Z1K (AKT mutation)
  Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Experimental: Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation)
  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.
• Experimental: Subprotocol Z1M (LAG-3 expression >= 1%)
  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.

Primary Outcome Measure

Objective response rate (ORR) [ Time Frame: Up to 3 years ]

Locations (1407)