Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors

Revolution Medicines

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Non-Small Cell Lung Cancer (NSCLC); Pancreatic Ductal Adenocarcinoma; Colorectal Cancer

Treatments: Drug: Elironrasib; Drug: Daraxonrasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06128551

RMC-6291-101

Details and patient eligibility

About

This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.

Full description

This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.

The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.

Enrollment: 534 estimated patients

Sex: All

Ages: 18 to 125 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age

• Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

  1. Phase 1b Dose Escalation: solid tumors, previously treated
  2. Phase 1b Dose Expansion and Phase 2:

  i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.

• ECOG performance status 0 or 1

• Adequate organ function

Exclusion criteria

• Primary central nervous system (CNS) tumors
• Active brain metastases
• Known impairment of GI function that would alter the absorption
• Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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534 participants in 3 patient groups

Elironrasib Monotherapy

Experimental group

Description:

Phase 2 only

Treatment:

Drug: Elironrasib

Daraxonrasib Monotherapy

Experimental group

Description:

Phase 2 only

Treatment:

Drug: Daraxonrasib

Daraxonrasib + Elironrasib Combination

Experimental group

Description:

Phase 1b and 2

Treatment:

Drug: Daraxonrasib

Drug: Elironrasib