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J2453 - A Platform Study of RAS(ON) Inhibitors in Patients with Gastrointestinal Solid Tumors + RMC-GI-102 Subprotocol A + RMC-GI-102 Subprotocol B + RMC-GI-102 Subprotocol C + RMC-GI-102 Subprotocol D + RMC-GI-102 Subprotocol E + RMC-GI

Details

Status

open

Study Type

Interventional

Study Phase

I

Location(s)

The Johns Hopkins Hospital

1800 Orleans St Baltimore, MD 21287

Brief Summary

The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents to be evaluated in patients with RAS-mutated solid tumors with a focus on GI cancers.

This is an open-label platform study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC) or with novel agents, and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with RAS mutations will be specified in each subprotocol.

Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter 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. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma. Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Eligibility

Inclusion Criteria:

All Patients (unless otherwise noted): 1.18 years old or older 2. ECOG PS is 0 to 1 3. Adequate organ function as outlined by the study 4. Must have pathologically documented, pancreatic carcinoma with documented metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A and B) 5. Must have pathologically documented, poorly differentiated pancreatic carcinoma with documented metastatic disease (Subprotocol C) -