Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

Detailed Description
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This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Official Title
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Phase 1/1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

Conditions
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Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma, Advanced Solid Tumor

Intervention / Treatment
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* Drug: RMC-6291


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥18 years of age. Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments. ECOG performance status 0 or 1 Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation 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. Prior therapy with KRASG12C (ON) inhibitor Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RMC-6291<br>Dose Escalation and Dose Expansion | Drug: RMC-6291<br>* Oral tablet once or twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of participants with adverse events | up to 3 years | 
| Dose Limiting Toxicities | Number of participants with dose limiting toxicities | The first 21 days (i.e. Cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Blood Concentration of RMC-6291 | Cmax | 7 Cycles | 
| Time to Reach Maximum Blood Concentration of RMC-6291 | Tmax | 7 Cycles | 
| Area Under Blood Concentration Time Curve of RMC-6291 | AUC | 7 Cycles | 
| Elimination Half-Life of RMC-6291 | t1/2 | 7 Cycles | 
| Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing | accumulation ratio | 7 Cycles | 
| Overall Response Rate (ORR) | Overall response rate per RECIST v1.1 | 3 years | 
| Duration of Response (DOR) | Duration of response per RECIST v1.1 | 3 years | 
| Disease Control Rate (DCR) | Disease control rate per RECIST v1.1 | 3 years | 
| Time to Response (TTR) | Time to response per RECIST v1.1 | 3 years | 
| Progression-Free Survival (PFS) | Progression-free survival per RECIST v1.1 | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchial neoplasms, respiratory tract neoplasms, neoplasms by site, neoplasms, Colon Cancer, Rectal Cancer, respiratory tract diseases, RMC-6291, RAS(ON), KRAS, KRASG12C, KRASG12C(ON), Targeted therapy, Metastatic cancer, Lung Cancer, Lung Neoplasms, Thoracic Neoplasms, Non-small Cell Lung Cancer, Carcinoma, Non-Small Cell Lung, NSCLC, Colorectal Cancer, Colonic Neoplasms, CRC, Appendiceal Cancer, KRAS mutation, STK11/LKB1, KEAP1, lung disease, Pancreatic Cancer, Carcinoma, Pancreatic Ductal, PDAC, Gastrointestinal Neoplasms, Intestinal Neoplasms, Esophageal cancer, Ampullary cancer, Gastric Cancer, Gynecological Cancer, Ovarian Cancer, Endometrial Cancer