First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• RLY-2608 — DRUG
  RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
• Fulvestrant — DRUG
  500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).
• Palbociclib 125mg — DRUG
  125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
• Ribociclib 400mg — DRUG
  400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
• Ribociclib 600mg — DRUG
  600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
• PF-07220060 100mg — DRUG
  PF-07220060 100 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
• PF-07220060 300 mg — DRUG
  PF-07220060 300 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.

Study Details

This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors. It will also evaluate RLY-2608 in combination RLY-2608 + fulvestrant and in triple combination RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) or CDK4 inhibitor (PF-07220060) for patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2 parts: a dose escalation (Part 1) and a dose expansion (Part 2).

Key Dates

Start date

Dec 8, 2021

Status verified

Sep 2025

Primary completion

Apr 30, 2027

Completion

Apr 30, 2027

Study Design

Enrollment

930 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: RLY-2608 for patients with unresectable or metastatic solid tumors
  Multiple doses of RLY-2608 for oral administration.
• Experimental: RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancer
  Oral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation.
• Experimental: RLY-2608+fulvestrant+palbo125mg for HR+HER2- locally advanced metastatic breast cancer
  Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation.
• Experimental: RLY-2608+fulvestrant+ribo400mg for HR+HER2- locally advanced metastatic breast cancer
  Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation.
• Experimental: RLY-2608+fulvestrant+ribo600mg for HR+HER2- locally advanced metastatic breast cancer
  Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation.
• Experimental: RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancer
  Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation
• Experimental: RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancer
  Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation

Primary Outcome Measure

Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 as a single agent [ 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 ]

Central Contacts

• Relay Therapeutics Inc
  617-322-0731
  [email protected]

Locations (24)

Find similar trials in Tucson, AZ

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