A First-in-human Study of RLY-8161 in Advanced NRAS-Mutant Solid Tumors

Relay Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: NRAS Q61H; NRAS Q61K; NRAS Q61L; NRAS G12D; NRAS G13R; NRAS G13D; NRAS G12V; NRAS Q61R; Advanced NRAS-Mutant Solid Tumors; NRAS Mutation; Advanced NRAS-Mutant Melanoma

Treatments: Drug: RLY-8161

Study type: Interventional

Funder types: Industry

Identifiers

NCT07584226

RLY-8161-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

Part 1: RLY-8161 for participants with advanced NRAS-mutant solid tumors

Experimental group

Description:

Multiple doses of RLY-8161 for oral administration

Treatment:

Drug: RLY-8161

Part 2: RLY-8161 for participants with advanced NRAS-mutant solid tumors

Experimental group

Description:

Oral doses of RLY-8161 as determined during Part 1 Dose Escalation

Treatment:

Drug: RLY-8161