Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma, Advanced Solid Tumor
Conditions
Keywords
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, bronchial neoplasms, respiratory tract neoplasms, neoplasms by site, neoplasms, Colon Cancer, Rectal Cancer, lung disease, respiratory tract diseases, Pancreatic Cancer, Carcinoma, Pancreatic Ductal, PDAC, Gastrointestinal Neoplasms, Intestinal Neoplasms, Esophageal cancer, Ampullary cancer, Gastric Cancer, Gynecological Cancer, Ovarian Cancer, Endometrial Cancer
Brief summary
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
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.
Interventions
DRUGRMC-6291
Oral tablet once or twice a day
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
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | up to 3 years | Number of participants with adverse events |
| Dose Limiting Toxicities | The first 21 days (i.e. Cycle 1) | Number of participants with dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Blood Concentration Time Curve of RMC-6291 | 7 Cycles | AUC |
| Elimination Half-Life of RMC-6291 | 7 Cycles | t1/2 |
| Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing | 7 Cycles | accumulation ratio |
| Overall Response Rate (ORR) | 3 years | Overall response rate per RECIST v1.1 |
| Maximum Observed Blood Concentration of RMC-6291 | 7 Cycles | Cmax |
| Disease Control Rate (DCR) | 3 years | Disease control rate per RECIST v1.1 |
| Time to Response (TTR) | 3 years | Time to response per RECIST v1.1 |
| Progression-Free Survival (PFS) | 3 years | Progression-free survival per RECIST v1.1 |
| Duration of Response (DOR) | 3 years | Duration of response per RECIST v1.1 |
| Time to Reach Maximum Blood Concentration of RMC-6291 | 7 Cycles | Tmax |
Countries
Australia, Czechia, France, Italy, Malaysia, Poland, Serbia, Singapore, South Korea, Spain, Taiwan, Thailand, United States
Outcome results
None listed