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Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Active, not recruiting
Sponsor
Relay Therapeutics, Inc.

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.