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

Relay Therapeutics, Inc.41 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

PIK3CA Mutation Solid Tumor, Adult HER2-negative Breast Cancer Breast Cancer Metastatic Breast Cancer

Interventions

RLY-5836DRUG

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

FulvestrantDRUG

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.

PalbociclibDRUG

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.

RibociclibDRUG

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.

AbemaciclibDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 RLY-5836 single agent arm key inclusion criteria * 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 Combination arms key inclusion criteria * 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%.

Locations (7)

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, United States

Community Cancer Center North

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Memorial Sloan Kettering Cancer Center-Main Campus

New York, New York, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of RLY-5836

Time frame: Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months

Number of participants with any dose-limiting toxicity (DLT)

Time frame: Cycle 1, up to 28 days.

Number of participants with adverse events (AEs)

Time frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months

Number of participants with serious adverse events (SAEs)

Time frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months

Secondary Outcomes

PIK3CA genotype in blood and tumor tissue by next generation nucleic acid sequencing

Time frame: Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months

PK of RLY-5836: area under the concentration-time curve (AUC)