Clinical Trial 23309

• Overview

  Study Title:

  A Platform Study of RAS(ON) Inhibitors to Treat Patients with Gastrointestinal Solid tumor - SUB-A: Study of RMC-6236 in Combination with 5-flourouracil-based regimens in Patients with Unresectable or Metastatic Colorectal Cancer or Metastatic Pancreatic Ductal Adenocarcinoma, - SUB: Study of RMC-6236 in Combination with Cetuximab with or without mFOLFOX6 in Patients with Unresectable or Metastatic Colorectal Cancer or Metastatic Pancreatic Ductal Adenocarcinoma, - SUB-C: Study of RMC-6236 in Combination with Gemcitabine and Nab-paclitaxel in Patients with Metastatic Pancreatic Ductal Adenocarcinoma - SUB-D: Study of RMC-9805 with or without RMC-6236 in Combination with 5-flourouracil-based Therapies in Patients with RAS G12D-Mutant Unresectable or Metastatic Colorectal Cancer or Metastatic Pancreatic Ductal Adenocarcinoma - SUB-E: Study of RMC-9805 with or without RMC-6236 in Combination with Cetuximab-based Therapies in Patients with RAS G12D-Mutant Unresectable or Metastatic Colorectal Cancer or Metastatic Pancreatic Ductal Adenocarcinoma - SUB-F: Study of RMC-9805 With or Without RMC-6236 in Combination with Gemcitabine and Nab-Paclitaxel in Patients with RAS G12D-Mutant Metastatic Pancreatic Ductal Adenocarcinoma

  Summary:

  The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents.

  Objective:

  SUB-A PRIMAY: Evaluate safety+tolerability of RMC-6236 in combo w/mFOLFIRINOX or mFOLFOX6 in pts w/mPDAC or combo w/mFOLFOX6+bevacizumab in pts w/RASmutant unresectable or mCRC. Define RP2D for RMC-6236 in combo w/mFOLFIRINOX or mFOLFOX6 in pts w/mPDAC or combo w/mFOLFOX6+bevacizumab in pts w/RAS-mutant unresectable or mCRC. Define RP2D for RMC-6236 combo w/mFOLFIRINOX in pts w/MPDAC. 2ND: PK of RMC-6236 combo w/mFOLFIRINOX in pts w/mPDAC or combo w/mFOLFOX6+bevacizumab in pts w/RAS-mutant unresectable or mCRC. Evaluate antitumor activity of RMC-6236 combo in pts w/treatment-naïve RASmutant unresectable or mCRC (mFOLFOX6+bevacizumab), in treatment naïve mPDAC (mFOLFIRINOX or mFOLFOX6). SUB-B PRIMARY: Evaluate safety+tolerability of RMC-6236 combo w/cetuximab-based regimens w/or w/o mFOLFOX6 in pts w/RAS-mutant unresectable or mCRC or w/cetuximab alone in pts w/mPDAC. Define RP2D for RMC-6236 combo w/cetuximab in pts w/mPDAC or combo w/cetuximab w/or w/o mFOLFOX6 in RAS-mutant unresectable or mCRC. 2ND: PK of RMC-6236 combo w/mFOLFIRINOX in pts w/mPDAC or combo w/mFOLFOX6+cetuximab in pts w/mPDAC or combo w/cetuximab w/or w/o mFOLFOX6 in RAS-mutant unresectable or mCRC. Evaluate antitumor activity of RMC-6236 combo in pts w/treatment-naïve RAS-mutant unresectable or mCRC, in previously treated pts w/RAS-mutant unresectable or mCRC, in previously treated pts w/mPDAC & in treatment-naïve pts w/mPDAC. SUB-C PRIMARY: Evaluate safety+tolerability of RMC-6236 combo w/GnP in pts w/mPDAC. Define RP2D for RMC-6236 combo wGnP in pts w/mPDAC. 2ND: PK of RMC-6236 combo w/GnP. Evaluate antitumor activity of RMC-6236 combo in pts w/treatment-naïve mPDAC. SUB-D PRIMARY: Evaluate safety+tolerability of RMC-9805 w/or w/o RMC-6236 in combo w/mFOLFIRINOX in pts w/RASG12D-mutant mPDAC. Evaluate safety+tolerability of RMC-9805 w/or w/o RMC-6236 combo w/mFOLFOX6+bevacizumab in pts w/RASG12D-mutant unresectable or mCRC. Determine RP2D of RMC-9805 w/or w/o RMC-6236 combo w/mFOLFIRINOX in pts w/RASG12D-mutant mPDAC. Determine RP2D of RMC-9805 w/or w/o RMC-6236 combo w/mFOLFOX6+bevacizumab in pts w/RASG12D-mutant unresectable or mCRC. 2ND: PK of RMC-9805 & RMC-6236 (if given) combo w/mFOLFIRINOX in pts w/RASG12D-mutant mPDAC. PK of RMC-9805 & RMC-6236 (if given) combo w/mFOLFOX6+bevacizumab in pts w/RASG12D-mutant unresectable or mCRC. Evaluate antitumor activity of RMC-9805 w/or w/o RMC-6236 combo w/mFOLFIRINOX in pts w/RASG12D-mutant mPDAC. Evaluate antitumor activity of RMC-9805 w/or w/o RMC-6236 combo w/mFOLFOX6+bevacizumab in pts w/RASG12D-mutant unresectable or mCRC. SUB-E PRIMARY: Evaluate safety+tolerability of RMC-9805 w/or w/o RMC-6236 combo w/cetuximab w/or w/o mFOLFOX6 in pts w/RASG12D-mutant unresectable or mCRC. Evaluate safety+tolerability of RMC-9805 combo w/cetuximab w/or w/o mFOLFOX6 in pts w/RASG12D-mutant mPDAC. Determine RP2D for RMC-9805 w/or w/o RMC-6236 combo w/cetuximab in pts w/RASG12D-mutant unresectable or mCRC. Determine RP2D for RMC-9805 w/or w/o RMC-6236 combo w/cetuximab+mFOLFOX6 in pts w/RASG12D-mutant unresectable or mCRC. 2ND: PK of RMC-9805 & RMC-6236 (if administered) combo w/cetuximab w/or w/o mFOLFOX6 in pts w/RASG12D-mutant unresectable or mCRC. PK of RMC-9805 combo w/cetuximab w/or w/o mFOLFOX6 in pts w/RASG12D-mutant mPDAC. Evaluate antitumor activity of RMC-9805 w/or w/o RMC-6236 combo w/cetuximab w/or w/o mFOLFOX6 in pts w/RASG12D-mutant unresectable or mCRC. Evaluate antitumor activity of RMC-9805 combo w/cetuximab w/or w/o mFOLFOX6 in pts w/RASG12D-mutant mPDAC. SUB-F PRIMARY: Evaluate safety+tolerability of RMC-9805 w/or w/o RMC-6236 combo w/GnP in pts w/RASG12D-mutant mPDAC. Determine RP2D for RMC-9805 w/or w/o RMC-6236 combo w/GnP in pts w/RASG12D-mutant mPDAC. 2nd: PK of RMC-9805 & RMC-6236 (if administered) combo w/GnP in pts w/RASG12D-mutant mPDAC. Evaluate antitumor activity of RMC-9805 w/or w/o RMC-6236 combo w/GnP in pts w/RASG12D-mutant mPDAC.

• Treatments

  Therapies:

  Chemotherapy (NOS); Therapy (NOS)

  Medications:

  5-fluorouracil (); Avastin (Bevacizumab); Bevacizumab (); CPT-11 (irinotecan); Camptosar (irinotecan); Cetuximab (); Daraxonrasib (); Erbitux (Cetuximab); Gemzar (gemcitabine); Nab-paclitaxel (Abraxane); Oxaliplatin (); RMC-6236 (); RMC-9805 (); Zoldonrasib (); eloxatin (Oxaliplatin); gemcitabine (); irinotecan (); leucovorin (); mFOLFIRINOX (); mFOLFOX6 ()

• Inclusion Criteria

  Inclusion Criteria: All Patients unless otherwise noted:
  • 18 years of age or older
  • Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 to 1
  • Adequate organ function as outlined by the Study
  • Pathologically or cytologically documented pancreatic carcinoma or poorly differentiated pancreatic carcinoma with metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A, B, and C)
  • Other criteria may apply

• Exclusion Criteria

  Exclusion Criteria: All Patients:
  • Primary central nervous system (CNS) tumors
  • Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
  • Major surgery within 28 days of first dose
  • Other criteria may apply

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