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Completed

NCT Number: NCT05759949

First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other 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).

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Key information

Conditions

PIK3CA Mutation Advanced Breast Cancer Breast Cancer Breast Diseases Breast Neoplasms HER2-negative Breast Cancer Hormone Receptor Positive Tumor Metastatic Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases Solid Tumor, Adult Unresectable Solid Tumor

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Sarah Cannon Research Institute at Florida Cancer Specialists, Orlando, Florida, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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%.

Treatment and study plan

RLY-5836

Drug

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

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.

Other names: Faslodex

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.

Other names: Ibrance

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.

Other names: Kisqali

Abemaciclib

Drug

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

Other names: Verzenio

Primary outcomes

  1. 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

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

    Time frame: Cycle 1, up to 28 days.

  3. Number of participants with adverse events (AEs)

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

  4. Number of participants with serious adverse events (SAEs)

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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

Sponsors and collaborators

Lead sponsor

Relay Therapeutics, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Mar 8, 2023
Registry last updated
May 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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