Purpose

This is an open-label, FIH study designed to evaluate the maximum tolerated 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 both RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors and RLY-2608 + fulvestrant combination arm for patients with HR+ HER2- locally advanced or metastatic breast cancer. This 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

Part 1- Evaluable disease per RECIST Version 1.1 Part 2 - Measurable disease per RECIST Version 1.1 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 - Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment. Part 1 - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively. Key Inclusion for RLY-2608 Single Agent Arm - Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy. Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types: Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations Key Inclusion for RLY-2608 + Fulvestrant Arm - Male or postmenopausal female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative therapy and must have been previously treated with GnRH agonist at least 4 weeks prior to start of study drug [ For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast cancer with: 1. ≤1 chemotherapy regimen, 2. ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and 3. ≥1 antiestrogen therapy including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane) [For Part 2, Group 2]: Received prior treatment with a PI3Kα inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.

Exclusion Criteria

Prior treatment with PI3Kα inhibitors (except for RLY-2608 + fulvestrant arm, Part 2, Group 2). Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%. History of hypersensitivity to PI3K inhibitors QT interval corrected using Fridericia's formula (QTcF) > 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
RLY-2608 Single Agent Arm: Part 1(multiple ascending doses, QD or BID):unresectable or metastatic solid tumors with PIK3CA mutation per local assessment; Part 2 (RP2D determined in Part 1) Patients with the following unresectable or metastatic solid tumors with ≥1 PIK3CA mutation per local assessment will be enrolled protocol defined groups RLY-2608+Fulvestrant Arm Part 1(multiple ascending doses, QD or BID): HR+, HER2- advanced or metastatic breast cancer with PIK3CA mutation per local assessment Part 2 (RP2D determined in Part 1) Group 1: patients who have not received prior PI3Kα inhibitor Group 2: patient who are intolerant to PI3Kα inhibitor
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
RLY-2608 for patients with unresectable or metastatic solid tumors
Multiple doses of RLY-2608 for oral administration.
  • Drug: RLY-2608
    RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
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.
  • Drug: RLY-2608
    RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
  • Drug: Fulvestrant
    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).
    Other names:
    • Faslodex

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Relay Therapeutics, Inc.

Study Contact

Relay Therapeutics Inc
617-322-0731
ClinicalTrials@relaytx.com

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.