Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer (NSCLC), NSCLC, Colorectal Cancer (CRC), CRC
Conditions
Keywords
Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer, NSCLC, Colorectal Cancer, CRC, RAS, NRAS, KRAS, HRAS, RAS Mutation
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation.
Detailed description
This is an open-label, multicenter, Phase 1/2 study of RAS(ON) inhibitors in combination with ivonescimab with or without other anti-cancer agents in adults with advanced or metastatic solid tumors with a RAS mutation to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: Arm A:daraxonrasib in combination with ivonescimab; Arm B: elironrasib in combination with ivonescimab; and Arm C: zoldonrasib in combination with ivonescimab. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Part 1 dose exploration will explore the safety and tolerability of individual RAS(ON) inhibitors in combination with ivonescimab. Part 2 dose expansion will explore the safety, tolerability, and antitumor activity of the individual RAS(ON) inhibitors with ivonescimab +/- anti-cancer therapies.
Interventions
DRUGDaraxonrasib
oral tablets
DRUGElironrasib
oral tablets
DRUGZoldonrasib
oral tablets
DRUGIvonescimab
IV infusion
DRUGCarboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)
IV infusion
DRUGcetuximab (Cohort C2 Only)
IV infusion
DRUGCarboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)
IV infusion
DRUGDaraxonrasib (Cohort B1 only)
oral tablets
Sponsors
Revolution Medicines, Inc.
Summit Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old and has provided informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Histologically confirmed, locally advanced or metastatic solid tumor malignancy with documented RAS mutation in KRAS, HRAS, or NRAS. * Received and progressed or been intolerant to prior standard therapy (Part 1 Dose Exploration). * Non-squamous NSCLC without a treatable driver mutation in other oncogenes that has not received prior systemic treatment (Arms A \& B for Part 2 Dose Expansion). * Solid tumor or CRC previously treated with no more than 2 prior lines of therapy for advanced disease and progressed or been intolerant to prior standard therapies (Arm C for Part 2 Dose Expansion). * Measurable disease per RECIST v1.1 * Adequate organ function (bone marrow, liver, kidney, coagulation, endocrine). * Able to take oral medications.
Exclusion criteria
* Head and neck squamous cell carcinoma. * Any conditions that may affect the ability to take or absorb study drug. * Major surgery within 4 weeks prior to receiving study drug(s). * Patient is unable or unwilling to comply with protocol-required study visits or procedures. * Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with adverse events (AEs) | Up to approximately 4 years | Number of patients with AEs as assessed by CTCAE v5. |
| Changes in vital signs | Up to approximately 4 years | Number of patients with changes in vital signs. |
| Changes in clinical laboratory test values | Up to approximately 4 years | Number of patients with changes in clinical laboratory test values. |
| Dose Limiting Toxicities | 28 days | Number of patients with dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of RAS(ON) inhibitors and ivonescimab | Up to Cycle 6 Day 1 (each cycle is 21 days) | Trough and peak blood concentrations of RAS(ON) inhibitors and ivonescimab over time as applicable. |
| Objective Response Rate (ORR) | Up to approximately 4 years | ORR per response evaluation criteria in solid tumors (RECIST) v1.1 |
| Duration of Response (DOR) | Up to approximately 4 years | DOR per RECIST v1.1 |
| Disease Control Rate (DCR) | Up to approximately 4 years | DCR per RECIST v1.1 |
| Time to response (TTR) | Up to approximately 4 years | TTR per RECIST v1.1 |
| Progression free survival (PFS) | Up to approximately 4 years | PFS per RECIST v1.1 |
| Anti-drug Antibody (ADA) of ivonescimab | Up to approximately 4 years | Number and percentage of patients with anti-ivonescimab antibody |
Countries
United States
Contacts
CONTACTRevolution Medicines Study Director
Outcome results
None listed