Actively Recruiting
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent and in Combination With Endocrine Therapy Plus or Minus a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer
Led by Relay Therapeutics, Inc. · Updated on 2025-09-22
930
Participants Needed
37
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating RLY-2608, a mutant-selective oral PI3Kα inhibitor, in patients with advanced solid tumors that have a PIK3CA mutation. The study also assesses RLY-2608 combined with fulvestrant alone or together with a CDK4/6 or CDK4 inhibitor in patients with hormone receptor-positive, HER2-negative advanced breast cancer. This first-in-human, open-label phase 1 trial aims to find the maximum tolerated dose, recommended phase 2 dose, safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-cancer activity of these treatments. The trial includes multiple treatment arms: RLY-2608 alone, RLY-2608 plus fulvestrant, and triple combinations of RLY-2608 with fulvestrant and either palbociclib, ribociclib, or PF-07220060. Dose escalation occurs first to identify safe dosing, followed by dose expansion phases. Treatments involve oral administration of RLY-2608 and the CDK inhibitors, while fulvestrant is given by intramuscular injection on specified days of each 28-day cycle. The combinations and doses are adjusted based on the results from the initial dose escalation phase. Participants will undergo regular assessments including tumor response evaluations, blood tests for pharmacokinetics and biomarkers, and monitoring of blood glucose and insulin levels. Safety is tracked through adverse event reporting every 4-week cycle, lasting approximately 24 months or until study discontinuation. Researchers will measure response rates and duration by RECIST criteria every 8 to 12 weeks over about 36 months. The study also monitors pharmacodynamic changes and gene mutation status using tumor and blood samples to understand treatment effects.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patient has ECOG performance status of 0-1
- One or more documented oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment
- Ability to provide archived tumor tissue or willingness to undergo pretreatment tumor biopsy (Part 1)
- Submit tumor tissue prior to study drug initiation for PIK3CA mutation determination (Part 2)
- Evaluable or measurable disease per RECIST v1.1 depending on study part
- Disease refractory to, intolerant of, or declined standard therapy
- For single agent arm: unresectable or metastatic solid tumor with specific group classifications
- For combination arms: histologically confirmed HR+, HER2- unresectable or metastatic breast cancer
- Premenopausal or perimenopausal females must be on GnRH agonist treatment before and during study
- Previous treatments for breast cancer allowed with specific limits depending on arm and group
You will not qualify if you...
- Prior treatment with PI3Kα, AKT, or mTOR inhibitors except specific arms/groups
- Prior treatment with immune checkpoint inhibitors
- For certain arms: prior systemic chemotherapy or antibody drug conjugate for advanced disease
- Prior treatment with CDK2, CDK4, or CDK4/6 inhibitors for advanced disease in some groups
- Prior fulvestrant or selective ER degrader treatment except limited neoadjuvant use
- Type 1 or 2 diabetes requiring antihyperglycemic medication or high blood sugar/HbA1c levels
- Allergy or hypersensitivity to study drug components
- Past or ongoing interstitial lung disease or pneumonitis needing intervention
- Cardiac criteria including prolonged QT interval
- CNS metastases or primary CNS tumor with progressive neurological symptoms
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until study discontinuation, approximately 24 months
Participants receive oral RLY-2608 alone or in combination with endocrine therapy and/or CDK4/6 or CDK4 inhibitors depending on their assigned group. Treatment cycles last 28 days and continue until study discontinuation.
Visits every 2 weeks during Cycle 1, then every cycle (28 days) thereafter
Duration - Up to 12 months after treatment ends, approximately
Participants are monitored after treatment ends for ongoing assessments of response and safety.
Visits approximately every 12 weeks
Trial Site Locations
Total: 37 locations
1
The University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
Actively Recruiting
2
University of California-San Diego
San Diego, California, United States, 90293
Actively Recruiting
3
HealthONE
Denver, Colorado, United States, 80218
Actively Recruiting
4
Yale University
New Haven, Connecticut, United States, 06510
Actively Recruiting
5
Florida Cancer Specialists
Orlando, Florida, United States, 32827
Actively Recruiting
6
Boca Raton Clinical Research (BRCR) Global
Plantation, Florida, United States, 33322
Withdrawn
7
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Actively Recruiting
8
Community Health Network
Indianapolis, Indiana, United States, 46250
Actively Recruiting
9
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Actively Recruiting
10
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
11
University of Michigan
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
12
Washington University School of Medicine St. Louis
St Louis, Missouri, United States, 63110
Actively Recruiting
13
Renown Regional Medical Center
Reno, Nevada, United States, 89502
Actively Recruiting
14
Rutgers University
New Brunswick, New Jersey, United States, 08901
Actively Recruiting
15
NYU Langone
New York, New York, United States, 10016
Actively Recruiting
16
Columbia University Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
Actively Recruiting
17
Memorial Sloan Kettering
New York, New York, United States, 10065
Actively Recruiting
18
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Actively Recruiting
19
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
Actively Recruiting
20
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
21
University of Utah- Huntsman Cancer Center
Salt Lake City, Utah, United States, 84112
Actively Recruiting
22
Inova Schar Cancer Center
Fairfax, Virginia, United States, 22031
Actively Recruiting
23
NEXT Virginia
Fairfax, Virginia, United States, 22301
Actively Recruiting
24
UW Carbone Cancer Center
Madison, Wisconsin, United States, 53792
Actively Recruiting
25
St Vincents Hospital
Sydney, New South Wales, Australia, 2019
Actively Recruiting
26
Peter MacCallum Cancer Center
Melbourne, Victoria, Australia, 3000
Actively Recruiting
27
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Actively Recruiting
28
Centre Léon Bérard
Lyon, Auvergne-Rhône-Alpes, France, 69008
Actively Recruiting
29
Institute Bergonié
Bordeaux, France, 33076
Actively Recruiting
30
Gustave Roussy
Villejuif, France, 94805
Actively Recruiting
31
Istituto Europeo di Oncologia IRCCS
Milan, Italy, 20141
Actively Recruiting
32
Vall d'Hebron Instituto de Oncologia
Barcelona, Barcelona, Spain, 08035
Actively Recruiting
33
START Barcelona
Barcelona, Catalonia, Spain, 08023
Actively Recruiting
34
Instituto Valenciano de Oncologia
Valencia, Valencia, Spain, 46009
Actively Recruiting
35
Institut Catala D'Oncologia - Badalona (ICO Badalona)
Barcelona, Spain, 08916
Actively Recruiting
36
START Madrid - Hospital Fundacion Jimenez Diaz
Madrid, Spain, 28040
Actively Recruiting
37
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Actively Recruiting
Research Team
R
Relay Therapeutics Inc
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
7
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