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

NCT05759949 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: RLY-5836-101
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 7

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (4)

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

  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)

  Cycle 1, up to 28 days.

• Number of participants with adverse events (AEs)

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

• Number of participants with serious adverse events (SAEs)

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

Secondary Outcomes (13)

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

  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)

  Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months

• PK of RLY-5836: maximum plasma concentration (Cmax)

  Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months

• PK of RLY-5836: time to maximum concentration (tmax)

  Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months

• PK of RLY-5836: half-life (t½)

  Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months

Study Arms (5)

RLY-5836 Single Agent Arm

EXPERIMENTAL

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

Drug: RLY-5836

RLY-5836 + Fulvestrant Arm

EXPERIMENTAL

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

Drug: RLY-5836; Drug: Fulvestrant

RLY-5836 + Palbociclib + Fulvestrant Arm

EXPERIMENTAL

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

Drug: RLY-5836; Drug: Fulvestrant; Drug: Palbociclib

RLY-5836 + Ribociclib + Fulvestrant Arm

EXPERIMENTAL

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

Drug: RLY-5836; Drug: Fulvestrant; Drug: Ribociclib

RLY-5836 + Abemaciclib + Fulvestrant Arm

EXPERIMENTAL

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

Drug: RLY-5836; Drug: Fulvestrant; Drug: Abemaciclib

Interventions

RLY-5836 DRUG

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

RLY-5836 + Abemaciclib + Fulvestrant Arm; RLY-5836 + Fulvestrant Arm; RLY-5836 + Palbociclib + Fulvestrant Arm; RLY-5836 + Ribociclib + Fulvestrant Arm; RLY-5836 Single Agent Arm

Fulvestrant 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.

Also known as: Faslodex

RLY-5836 + Abemaciclib + Fulvestrant Arm; RLY-5836 + Fulvestrant Arm; RLY-5836 + Palbociclib + Fulvestrant Arm; RLY-5836 + Ribociclib + Fulvestrant Arm

Palbociclib 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.

Also known as: Ibrance

RLY-5836 + Palbociclib + Fulvestrant Arm

Ribociclib 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.

Also known as: Kisqali

RLY-5836 + Ribociclib + Fulvestrant Arm

Abemaciclib DRUG

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

Also known as: Verzenio

RLY-5836 + Abemaciclib + Fulvestrant Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Relay Therapeutics, Inc.: lead

Study Sites (7)

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

Location

Community Cancer Center North

Indianapolis, Indiana, 46250, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Memorial Sloan Kettering Cancer Center-Main Campus

New York, New York, 10065, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; palbociclib; ribociclib; abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

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

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: March 8, 2023
• Study Start: March 29, 2023
• Primary Completion: March 18, 2025
• Study Completion: April 11, 2025
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)