First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer
Phase 1
Recruiting
- Conditions
- PIK3CA MutationSolid Tumor, AdultHER2-negative Breast CancerBreast CancerMetastatic Breast CancerAdvanced Breast CancerUnresectable Solid TumorEndometrial Cancer
- Interventions
- Drug: PF-07220060 100mgDrug: PF-07220060 300 mg
- Registration Number
- NCT05216432
- Lead Sponsor
- Relay Therapeutics, Inc.
- Brief Summary
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 or endometrial cancer (palbociclib or ribociclib Part 1). 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 890
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RLY-2608 for patients with unresectable or metastatic solid tumors RLY-2608 Multiple doses of RLY-2608 for oral administration. RLY-2608+fulvestrant+palbo125mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca Palbociclib 125mg Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo600mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca Ribociclib 600mg Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation. RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancer RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+palbo125mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+palbo125mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo400mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca Ribociclib 400mg Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation. RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancer Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo600mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo400mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo600mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo400mg for HR+HER2 locally advanced/metastatic breast cancer/endometrial ca Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancer RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancer PF-07220060 100mg Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancer Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancer RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancer Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancer PF-07220060 300 mg Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation
- Primary Outcome Measures
Name Time Method Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 as a single agent 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 Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant 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 Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant and a CDK 4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant 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 Number of patients with adverse events and serious adverse events of RLY-2608 as a single agent Every cycle (4-week cycles) until study discontinuation, approximately 24 months Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant Every cycle (4-week cycles) until study discontinuation, approximately 24 months Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant and a CDK 4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant Every cycle (4-week cycles) until study discontinuation, approximately 24 months
- Secondary Outcome Measures
Name Time Method PIK3CA gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue Day 1 of Cycle 1 (each cycle is 28 days) Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) as single agent Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including area under the plasma concentration versus time curve during a dose interval (AUC0-tau) of RLY-2608 (and its metabolites, as appropriate) as single agent Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) as single agent Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including area under the plasma concentration versus time curve during a dose interval (AUC0-tau) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months PK parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant + palbociclib or ribociclib. And in combination (PF-07220060) +fulvestrant Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including area under the plasma concentration vs time curve of RLY-2608 (and its metabolites, as appropriate) administered with fulvestrant + palbociclib or ribociclib, and in combination with PF-07220060 +fulvestrant Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Pharmacokinetic parameters including half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant + palbociclib or ribociclib, and in combination with PF-07220060 +fulvestrant Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months Changes in circulating blood of fasting glucose in RLY-2608 as a single agent Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of insulin in RLY-2608 as a single agent Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of C-peptide in RLY-2608 as a single agent Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of HbA1c in RLY-2608 as a single agent Once in Cycle 2 (4-week cycle) and then once every 3rd cycle beginning with Cycle 5 through end of treatment, approximately 24 months Changes in circulating blood of fasting glucose in RLY-2608 in combination with fulvestrant Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of insulin in RLY-2608 in combination with fulvestrant Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of C-peptide in RLY-2608 in combination with fulvestrant Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of HbA1c in RLY-2608 in combination with fulvestrant Once in Cycle 2 (4-week cycle) and then once every 3rd cycle beginning with Cycle 5 through end of treatment, approximately 24 months Changes in circulating blood of fasting glucose in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib) and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of insulin in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of C-peptide in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months Changes in circulating blood of HbA1c in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant Once in Cycle 2 (4-week cycle) and then once every 3rd cycle beginning with Cycle 5 through end of treatment, approximately 24 months Disease Control Rate (DCR) as assessed by RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Once every cycle (4-week cycles) through end of treatment, approximately 24 months Objective response rate (ORR) as assessed by RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Duration of Response (DOR) as assessed by RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Clinical benefit rate (CBR) as assessed by RECIST v1.1 [Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months]
Trial Locations
- Locations (36)
HealthONE
🇺🇸Denver, Colorado, United States
START Barcelona
🇪🇸Barcelona, Catalonia, Spain
Institut Catala D'Oncologia - Badalona (ICO Badalona)
🇪🇸Barcelona, Spain
START Madrid - Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Yale University
🇺🇸New Haven, Connecticut, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
University of Utah- Huntsman Cancer Center
🇺🇸Salt Lake City, Utah, United States
Inova Schar Cancer Center
🇺🇸Fairfax, Virginia, United States
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of California-San Diego
🇺🇸San Diego, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Gustave Roussy
🇫🇷Villejuif, France
Vall d'Hebron Instituto de Oncologia
🇪🇸Barcelona, Spain
Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
Boca Raton Clinical Research (BRCR) Global
🇺🇸Plantation, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
St Vincents Hospital
🇦🇺Sydney, New South Wales, Australia
Community Health Network
🇺🇸Indianapolis, Indiana, United States
Rutgers University
🇺🇸New Brunswick, New Jersey, United States
UW Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
NYU Langone
🇺🇸New York, New York, United States
Washington University School of Medicine St. Louis
🇺🇸Saint Louis, Missouri, United States
Columbia University Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
Peter MacCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia
Institute Bergonié
🇫🇷Bordeaux Cedex, France
Istituto Europeo di Oncologia IRCCS
🇮🇹Milano, Italy