A First-in-human Study of RLY-8161 in Advanced NRAS-Mutant Solid Tumors
Purpose
This is a Phase 1 first-in-human, open-label multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of RLY-8161, an NRAS-selective inhibitor, in participants with advanced NRAS-mutant melanoma and other solid tumors.
Conditions
- NRAS Mutation
- NRAS-mutant Advanced Melanoma
- NRAS-mutant Solid Tumors
- NRAS Q61R
- NRAS Q61K
- NRAS Q61L
- NRAS Q61H
- NRAS G12D
- NRAS G13R
- NRAS G13D
- NRAS G12V
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. - Histologically confirmed diagnosis of unresectable Stage III or IV melanoma or other solid tumor. - Disease is refractory to standard therapy (including targeted therapy), participant is intolerant of standard therapy, or participant has declined standard therapy. - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - One or more documented primary oncogenic NRAS mutation(s).
Exclusion Criteria
- Known activating KRAS, HRAS, or BRAF mutation or known alterations in other driver oncogenes. - Prior treatment with ERK, MEK, RAF, or RAS targeting agents or any agent whose mechanism of action is to inhibit the RAS-MAPK pathway. - For participants with melanoma: lactate dehydrogenase (LDH) >2×ULN. - Central nervous system (CNS) metastases that are associated with progressive neurologic symptoms or require ongoing corticosteroids to control the CNS disease.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1: RLY-8161 for participants with advanced NRAS-mutant solid tumors |
Multiple doses of RLY-8161 for oral administration |
|
|
Experimental Part 2: RLY-8161 for participants with advanced NRAS-mutant solid tumors |
Oral doses of RLY-8161 as determined during Part 1 Dose Escalation |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Relay Therapeutics, Inc.
Detailed Description
This is a Phase 1 first-in-human, open-label multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of RLY-8161, an NRAS-selective inhibitor, in participants with advanced NRAS-mutant melanoma and other solid tumors. This study consists of 2 parts: dose escalation (Part 1) and dose expansion (Part 2). Part 1, dose escalation will explore multiple ascending doses of RLY-8161 in participants with any advanced NRAS-mutant solid tumor until maximum tolerated dose is reached or one or more recommended Phase 2 dose (RP2D) is identified. Part 2, dose expansion will be at the RP2D(s) identified in Part 1 in NRAS-mutant solid tumors.