Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors
Conditions
Keywords
KRAS, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, NSCLC, CRC, PDAC, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Colorectal Neoplasms, Colonic Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplastic Processes, Thoracic Neoplasms, Antineoplastic Agents, Melanoma, Gynecological Cancers, RAS
Brief summary
Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.
Detailed description
This is a Phase 1/2, multicenter open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult patients with advanced solid tumors harboring specific RAS mutations, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose \[RP2D\] within investigated patient population groups. RMC-6236 is a potent, orally bioavailable RAS-MULTI(ON) inhibitor, selective for the active RAS(ON) form of both wild type and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS).
Interventions
DRUGRMC-6236
Oral Tablets
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion). * Treatment naive or have received prior standard therapy appropriate for tumor type and stage * Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ function
Exclusion criteria
* Primary central nervous system (CNS) tumors * Active, untreated brain metastases * Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication * History of any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy Other inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs | up to 2.5 years |
| Number of Participants with Dose-Limiting Toxicity (DLT) | 21 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Blood Concentration Time Curve (AUC) of RMC-6236 | up to 15 weeks | — |
| Elimination Half-Life of RMC-6236 (t1/2) | up to 15 weeks | — |
| Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing | up to 15 weeks | — |
| Overall Response Rate (ORR) | up to 2.5 years | Overall response rate per RECIST v1.1 |
| Maximum Observed Blood Concentration (Cmax) of RMC-6236 | up to 15 weeks | — |
| Disease Control Rate (DCR) | up to 2.5 years | Disease control rate per RECIST v1.1 |
| Time to Response (TTR) | up to 2.5 years | Time to response per RECIST v1.1 |
| Progression-Free Survival (PFS) | up to 2.5 years | Progression-free survival per RECIST v1.1 |
| Duration of Response (DOR) | up to 2.5 years | Duration of response per RECIST v1.1 |
| Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236 | up to 15 weeks | — |
Countries
United States
Contacts
Primary ContactRevolution Medicines, Inc.
Outcome results
None listed