Study of RMC-9805 in Participants With KRASG12D-Mutant Solid Tumors

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of RMC-9805 in adults with KRAS G12D-mutant solid tumors.

Detailed Description
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This is an open-label, multicenter, Phase 1/1b study of RMC-9805, monotherapy, selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two parts: Part 1- Dose-Exploration and Part 2- Dose-Expansion.

Official Title
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Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG12D-Mutant Solid Tumors

Conditions
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Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors

Intervention / Treatment
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* Drug: RMC-9805


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically documented, locally advanced or metastatic solid tumor malignancy with KRASG12D-mutations identified through deoxyribonucleic acid (DNA) sequencing or polymerase chain reaction (PCR) test Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage ECOG performance status 0 or 1 Adequate organ function Exclusion Criteria: Primary central nervous system (CNS) tumors Known or suspected leptomeningeal or active brain metastases or spinal cord compression Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication Participant was previously treated with an investigational KRASG12D inhibitor or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors) 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-9805<br>Dose exploration and dose expansion | Drug: RMC-9805<br>* Oral Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs | Up to 3 years | 
| Dose Limiting Toxicities | Number of participants with Dose Limiting Toxicities (DLTs) | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Blood Concentration (Cmax) of RMC-9805 | Cmax | up to 21 weeks | 
| Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 | Tmax | up to 21 weeks | 
| Area Under Blood Concentration Time Curve (AUC) of RMC-9805 | AUC | up to 21 weeks | 
| Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing | accumulation ratio of RMC-9805 | up to 21 weeks | 
| Elimination Half-Life (t1/2) of RMC-9805 | t1/2 | up to 21 weeks | 
| Overall Response Rate (ORR) | Assess per RECIST v1.1 | up to 3 years | 
| Duration of Response (DOR) | Assess per RECIST v1.1 | up to 3 years | 
| Disease Control Rate (DCR) | Assess per RECIST v1.1 | up to 3 years | 
| Time to Response (TTR) | Assess per RECIST v1.1 | up to 3 years | 
| Progression-Free Survival (PFS) | Assess per RECIST v1.1 | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, KRAS G12D (ON), NSCLC, PDAC, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer, Pancreatic Cancer, Metastatic Cancer, Pancreatic Ductal Adenocarcinoma, Pancreatic Neoplasms, Colorectal Neoplasms, Gastrointestinal Neoplasms, KRAS, Colonic Neoplasms