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

May 13, 2025 updated by: Relay Therapeutics, Inc.

A First-in-Human Study of PI3Kα Inhibitor, RLY-5836, in Combination With Targeted and Endocrine Therapies in Participants With Advanced Breast Cancer and as a Single Agent in Advanced Solid Tumors

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32827
        • Sarah Cannon Research Institute at Florida Cancer Specialists
    • Indiana
      • Indianapolis, Indiana, United States, 46250
        • Community Cancer Center North
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center-Main Campus
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute, University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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%.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RLY-5836 Single Agent Arm
RLY-5836 single agent arm for participants with unresectable or metastatic solid tumors
Drug: RLY-5836
RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.
Experimental: RLY-5836 + Fulvestrant Arm
RLY-5836 + fulvestrant combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer
Drug: RLY-5836
RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.
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.
Other Names:
  • Faslodex
Experimental: RLY-5836 + Palbociclib + Fulvestrant Arm
RLY-5836 + palbociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer
Drug: RLY-5836
RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.
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.
Other Names:
  • Faslodex
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.
Other Names:
  • Ibrance
Experimental: RLY-5836 + Ribociclib + Fulvestrant Arm
RLY-5836 + ribociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer
Drug: RLY-5836
RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.
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.
Other Names:
  • Faslodex
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.
Other Names:
  • Kisqali
Experimental: RLY-5836 + Abemaciclib + Fulvestrant Arm
RLY-5836 + abemaciclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer
Drug: RLY-5836
RLY-5836 is a mutant-selective, oral PI3Kα inhibitor.
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.
Other Names:
  • Faslodex
Drug: Abemaciclib
Abemaciclib 150 mg BID will be taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles.
Other Names:
  • Verzenio

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
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.
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
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
Every cycle (4-week cycles) until study discontinuation, approximately 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
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)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
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)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
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)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
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)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
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: clearance following oral dose (CL/F)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
Changes in circulating markers of glucose metabolism: changes in circulating glucose
Time Frame: Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Changes in circulating markers of glucose metabolism: changes in circulating insulin
Time Frame: Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Changes in circulating markers of glucose metabolism: changes in circulating C-peptide
Time Frame: Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Changes in circulating markers of glucose metabolism: changes in circulating glycosylated hemoglobin [HbA1c]
Time Frame: Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months
Preliminary antitumor activity of RLY-5836: duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
Time Frame: Approximately every 8 weeks until progressive disease, approximately 36 months
Approximately every 8 weeks until progressive disease, approximately 36 months
Preliminary antitumor activity of RLY-5836: disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
Time Frame: Approximately every 8 weeks until progressive disease, approximately 36 months
Approximately every 8 weeks until progressive disease, approximately 36 months
Preliminary antitumor activity of RLY-5836: objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
Time Frame: Approximately every 8 weeks until progressive disease, approximately 36 months
Approximately every 8 weeks until progressive disease, approximately 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Relay Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 29, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 18, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 11, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 23, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 7, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 8, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RLY-5836-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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