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

Phase 1RecruitingNCT07584226

Relay Therapeutics, Inc.35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced NRAS-Mutant Melanoma Advanced NRAS-Mutant Solid Tumors

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (6)

University of California, Los Angeles (UCLA) Department of Medicine

Los Angeles, California, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

START Midwest, LLC

Grand Rapids, Michigan, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

RECRUITING

Sarah Cannon Research Institute (SCRI) Oncology Partners

Nashville, Tennessee, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

RECRUITING

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

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

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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

Part 2: Progression-free survival (PFS) as assessed by RECIST v1.1

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

Part 2: Overall Survival

Time frame: Cycle 1 (28-day cycles) until study completion, approximately 30 months

Part 2: Number of participants with AEs or SAEs, with changes in vital signs, ECGs, and laboratory tests

Time frame: 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

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

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts