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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RMC-9805
Sponsored by
Revolution Medicines, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring KRAS G12D (ON), NSCLC, CRC, 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • STARTRecruiting
  • NEXT Oncology VirginiaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RMC-9805

Arm Description

Dose exploration and dose expansion

Outcomes

Primary Outcome Measures

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
Dose Limiting Toxicities
Number of participants with Dose Limiting Toxicities (DLTs)

Secondary Outcome Measures

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

Full Information

First Posted
August 31, 2023
Last Updated
September 8, 2023
Sponsor
Revolution Medicines, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT06040541
Brief Title
Study of RMC-9805 in Participants With KRASG12D-Mutant Solid Tumors
Official Title
Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG12D-Mutant Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2023 (Actual)
Primary Completion Date
August 30, 2025 (Anticipated)
Study Completion Date
July 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revolution Medicines, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors
Keywords
KRAS G12D (ON), NSCLC, CRC, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
290 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RMC-9805
Arm Type
Experimental
Arm Description
Dose exploration and dose expansion
Intervention Type
Drug
Intervention Name(s)
RMC-9805
Intervention Description
Oral Tablets
Primary Outcome Measure Information:
Title
Adverse events
Description
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs
Time Frame
Up to 3 years
Title
Dose Limiting Toxicities
Description
Number of participants with Dose Limiting Toxicities (DLTs)
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Maximum Observed Blood Concentration (Cmax) of RMC-9805
Description
Cmax
Time Frame
up to 21 weeks
Title
Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805
Description
Tmax
Time Frame
up to 21 weeks
Title
Area Under Blood Concentration Time Curve (AUC) of RMC-9805
Description
AUC
Time Frame
up to 21 weeks
Title
Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing
Description
accumulation ratio of RMC-9805
Time Frame
up to 21 weeks
Title
Elimination Half-Life (t1/2) of RMC-9805
Description
t1/2
Time Frame
up to 21 weeks
Title
Overall Response Rate (ORR)
Description
Assess per RECIST v1.1
Time Frame
up to 3 years
Title
Duration of Response (DOR)
Description
Assess per RECIST v1.1
Time Frame
up to 3 years
Title
Disease Control Rate (DCR)
Description
Assess per RECIST v1.1
Time Frame
up to 3 years
Title
Time to Response (TTR)
Description
Assess per RECIST v1.1
Time Frame
up to 3 years
Title
Progression-Free Survival (PFS)
Description
Assess per RECIST v1.1
Time Frame
up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Revolution Medicines, Inc.
Phone
(650) 779-2300
Email
CT-inquiries@RevMed.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Revolution Medicines, Inc.
Organizational Affiliation
Revolution Medicines, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
START
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
NEXT Oncology Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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