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

NCT07584226 | Recruiting Phase 1 FDA Drug

• 1 other identifier: RLY-8161-101
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 9

Brief Summary

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

Outcome Measures

Primary Outcomes (3)

• Part 1: Maximum Tolerated Dose (MTD) and/or RP2D of RLY-8161

  Cycle 1 (28-day cycle) of treatment for MTD and at the end of every cycle (28-day cycle) for RP2D until treatment discontinuation, approximately 12 months

• Part 1: Number of participants with Adverse Events (AEs) or Serious Adverse Events (SAEs), with changes in vital signs, electrocardiograms (ECGs), and laboratory tests

  Cycle 1 (28-day cycle) of treatment and at the end of every cycle (28-day cycle) until 30 days after treatment discontinuation, approximately 13 months

• Part 2: Objective Response Rate (ORR) of RLY-8161 as assessed by RECIST v1.1

  Approximately every 8 weeks on treatment and every 12 weeks after last dose in the absence of progressive disease, approximately 18 months

Secondary Outcomes (8)

• Part 1 and Part 2: Changes in NRAS mutant allele fraction in ctDNA

  Approximately every 2 weeks in Cycle 1 (28-day cycle), at the beginning of Cycle 2 (28-day cycle), and at the beginning of every odd cycle (28-day cycle) until End of Treatment (EOT), approximately 12 months

• Part 1 and Part 2: Plasma concentration and PK parameters of RLY-8161

  Approximately every 2 weeks in Cycle 1 (28-day cycle) and at Day 1 of every cycle (28-day cycle) through Cycle 4

• Part 1: ORR of RLY-8161 as assessed by RECIST v1.1

  Approximately every 8 weeks on treatment and every 12 weeks after last dose in the absence of progressive disease, approximately 18 months

• Part 1 and 2: Duration of Response (DOR) of RLY-8161 as assessed by RECIST v1.1

  Approximately every 8 weeks on treatment and every 12 weeks after last dose in the absence of progressive disease, approximately 18 months

• Part 1 and 2: Disease Control Rate (DCR) of RLY-8161 as assessed by RECIST v1.1

  Approximately every 8 weeks on treatment and every 12 weeks after last dose in the absence of progressive disease, approximately 18 months

Study Arms (2)

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

EXPERIMENTAL

Multiple doses of RLY-8161 for oral administration

Drug: RLY-8161

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

EXPERIMENTAL

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

Drug: RLY-8161

Interventions

RLY-8161 DRUG

RLY-8161 is an NRAS-selective inhibitor

Part 1: RLY-8161 for participants with advanced NRAS-mutant solid tumors; Part 2: RLY-8161 for participants with advanced NRAS-mutant solid tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Relay Therapeutics, Inc.: lead

Study Sites (9)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

START Midwest, LLC

Grand Rapids, Michigan, 49546, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Sarah Cannon Research Institute Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Central Study Contacts

Relay Therapeutics, Inc

CONTACT

617-322-0731; ClinicalTrials@relaytx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: May 13, 2026
• Study Start: March 9, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 2, 2026

Record last verified: 2026-06

Locations

US (9)