Arms |
Assigned Interventions |
Experimental:Subprotocol A (EGFR activating mutation)
Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Other:Laboratory Biomarker Analysis Undergo molecular analysis |
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.
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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.
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Drug:Crizotinib Given PO |
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.
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Experimental:Subprotocol E (EGFR T790M or rare activating mutation)
Patients with EGFR T790M or rare activating mutation receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Drug:Osimertinib Given PO |
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.
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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.
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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.
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Drug:Trametinib Given PO |
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.
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Drug:Taselisib Given PO |
Experimental:Subprotocol J (HER2 amplification >= 7 copy numbers)
Patients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
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Biological:Trastuzumab Emtansine Given IV |
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.
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Drug:Erdafitinib Given PO |
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.
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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.
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Drug:Sapanisertib Given PO |
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.
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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.
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Drug:PI3K-beta Inhibitor GSK2636771 Given PO |
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.
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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.
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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.
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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.
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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.
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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.
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Drug:Vismodegib Given PO |
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.
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Drug:Defactinib Hydrochloride Given PO |
Experimental:Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib malate PO QD for 4 weeks. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
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Drug:Sunitinib Malate Given PO |
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.
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Drug:FGFR Inhibitor AZD4547 Given PO |
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.
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Drug:Dasatinib Given PO |
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.
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Drug:Capivasertib Given PO |
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.
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Drug:Binimetinib Given PO |
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.
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Drug:Palbociclib Given PO |
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.
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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.
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Biological:Nivolumab Given IV |
Experimental:Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Drug:Larotrectinib Sulfate Given PO |
Experimental:Subprotocol Z1F (PIK3CA mutation)
Patients with PIK3CA 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.
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Drug:Copanlisib Hydrochloride Given IV |
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.
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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.
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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.
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Drug:Adavosertib Given PO |
Experimental:Subprotocol Z1K (AKT mutation)
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Drug:Ipatasertib Given PO |
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.
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Drug:Ulixertinib Give PO |