First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other Solid Tumors

NCT ID: NCT05759949

Last Updated: 2025-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-29

Study Completion Date

2025-04-11

Brief Summary

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This is a Phase 1, first-in-human, open-label study designed to evaluate the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RLY-5836 in advanced solid tumors in participants harboring a PIK3CA mutation in blood and/or tumor per local assessment. The study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).

Detailed Description

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Conditions

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PIK3CA Mutation Solid Tumor, Adult HER2-negative Breast Cancer Breast Cancer Metastatic Breast Cancer Advanced Breast Cancer Unresectable Solid Tumor Hormone Receptor Positive Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RLY-5836 Single Agent Arm

RLY-5836 single agent arm for participants with unresectable or metastatic solid tumors

Group Type EXPERIMENTAL

RLY-5836

Intervention Type DRUG

RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.

RLY-5836 + Fulvestrant Arm

RLY-5836 + fulvestrant combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group Type EXPERIMENTAL

RLY-5836

Intervention Type DRUG

RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.

Fulvestrant

Intervention Type DRUG

Fulvestrant (500 mg) is administered IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as 2×5 mL injections, 1 in each buttock, on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of each subsequent cycle.

RLY-5836 + Palbociclib + Fulvestrant Arm

RLY-5836 + palbociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group Type EXPERIMENTAL

RLY-5836

Intervention Type DRUG

RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.

Fulvestrant

Intervention Type DRUG

Fulvestrant (500 mg) is administered IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as 2×5 mL injections, 1 in each buttock, on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of each subsequent cycle.

Palbociclib

Intervention Type DRUG

Palbociclib 125 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

RLY-5836 + Ribociclib + Fulvestrant Arm

RLY-5836 + ribociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group Type EXPERIMENTAL

RLY-5836

Intervention Type DRUG

RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.

Fulvestrant

Intervention Type DRUG

Fulvestrant (500 mg) is administered IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as 2×5 mL injections, 1 in each buttock, on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of each subsequent cycle.

Ribociclib

Intervention Type DRUG

Ribociclib 600 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

RLY-5836 + Abemaciclib + Fulvestrant Arm

RLY-5836 + abemaciclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group Type EXPERIMENTAL

RLY-5836

Intervention Type DRUG

RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.

Fulvestrant

Intervention Type DRUG

Fulvestrant (500 mg) is administered IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as 2×5 mL injections, 1 in each buttock, on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of each subsequent cycle.

Abemaciclib

Intervention Type DRUG

Abemaciclib 150 mg BID will be taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles.

Interventions

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RLY-5836

RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.

Intervention Type DRUG

Fulvestrant

Fulvestrant (500 mg) is administered IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as 2×5 mL injections, 1 in each buttock, on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of each subsequent cycle.

Intervention Type DRUG

Palbociclib

Palbociclib 125 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

Intervention Type DRUG

Ribociclib

Ribociclib 600 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

Intervention Type DRUG

Abemaciclib

Abemaciclib 150 mg BID will be taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles.

Intervention Type DRUG

Other Intervention Names

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Faslodex Ibrance Kisqali Verzenio

Eligibility Criteria

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Inclusion Criteria

Patient has ECOG performance status of 0-1

One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment


* Disease that is refractory to standard therapy, intolerant to standard therapy, or participant has declined standard therapy.
* A histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor


* Males, postmenopausal females, or pre-/perimenopausal females previously treated with gonadotropin-releasing GnRH agonist at least 4 weeks prior to start of study drug with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy.
* Had previous treatment for advanced or metastatic breast cancer with antiestrogen therapy including, but not limited to, selective estrogen receptor degraders (e.g., fulvestrant), selective estrogen receptor modulators (e.g., tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane)
* Part 1: Prior PI3Kα inhibitor treatment is allowed if taken for \< 14 days and not discontinued due to disease progression, hypersensitivity, or ≥ Grade 3 TEAEs.

Exclusion Criteria

* Part 2: Prior treatment with PI3Kα inhibitors.
* Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Relay Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, United States

Site Status

Community Cancer Center North

Indianapolis, Indiana, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center-Main Campus

New York, New York, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

Other Identifiers

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RLY-5836-101

Identifier Type: -

Identifier Source: org_study_id

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