Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer, Pancreatic Ductal Adenocarcinoma
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, RMC-6236, Elironrasib, Daraxonrasib
Brief summary
This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.
Detailed description
This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity. The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.
Interventions
DRUGElironrasib
oral tablets
DRUGDaraxonrasib
oral tablets
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age * Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy 1. Phase 1b Dose Escalation: solid tumors, previously treated 2. Phase 1b Dose Expansion and Phase 2: i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors. * ECOG performance status 0 or 1 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with adverse events (AEs) in Phase 1b | Up to approximately 3 years | Incidence and severity of treatment-emergent AEs and serious AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 |
| Changes in vital signs in Phase 1b | Up to approximately 3 years | Number of patients with clinically significant changes in vital signs |
| Changes in clinical laboratory test values in Phase 1b | Up to approximately 3 years | Number of patients with clinically significant changes in clinical laboratory test values |
| Dose Limiting Toxicities in Phase 1b | 21 days | Number of participants with dose limiting toxicities |
| Changes in ECGs in Phase 1b | Up to approximately 3 years | Number of patients with clinically significant changes in ECGs |
| Overall Response Rate (ORR) in Phase 2 | Up to approximately 3 years | Overall response rate per RECIST v1.1 as assessed by blinded independent central review (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib | up to 21 weeks | Cmax |
| Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib | up to 21 weeks | Tmax |
| Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib | up to 21 weeks | AUC |
| Elimination Half-Life of Elironrasib and Daraxonrasib | up to 21 weeks | t1/2 |
| Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing | up to 21 weeks | accumulation ratio |
| Overall Response Rate (ORR) in Phase 1b | Up to approximately 3 years | Overall response rate per RECIST v1.1 |
| Duration of Response (DOR) | Up to approximately 3 years | Duration of response per RECIST v1.1 |
| Disease Control Rate in Phase 1b | Up to approximately 3 years | Disease Control rate per RECIST v1.1 |
| Time to Response (TTR) in Phase 1b | Up to approximately 3 years | Time to response per RECIST v1.1 |
| Progression-Free Survival (PFS) | Up to approximately 3 years | Progression-free survival per RECIST v1.1 |
| Number of patients with AEs in Phase 2 | Up to approximately 3 years | Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5 |
| Changes in vital signs in Phase 2 | Up to approximately 3 years | Number of patients with clinically significant changes in vital signs |
| Changes in clinical laboratory values in Phase 2 | Up to approximately 3 years | Number of patients with clinically significant changes in clinical laboratory test values |
| Overall Survival (OS) in Phase 2 | Up to approximately 3 years | OS is defined as time from enrollment until death from any cause |
Countries
France, Germany, Italy, Netherlands, Puerto Rico, Spain, United States
Contacts
CONTACTRevolution Medicines, Inc.
STUDY_DIRECTORRevolution Medicines, Inc.
Revolution Medicines, Inc.
Outcome results
None listed