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
Phase 1
Recruiting
- Conditions
- Solid Tumor, AdultHER2-negative Breast CancerBreast CancerPIK3CA MutationMetastatic Breast CancerAdvanced Breast CancerUnresectable Solid Tumor
- 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. 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
- 930
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 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 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+palbo125mg for HR+HER2- locally advanced metastatic breast cancer 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 Fulvestrant 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 Palbociclib 125mg 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 RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo400mg for HR+HER2- locally advanced metastatic breast cancer Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo400mg for HR+HER2- locally advanced metastatic breast cancer Ribociclib 400mg 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 RLY-2608 Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo600mg for HR+HER2- locally advanced metastatic breast cancer Fulvestrant Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation. RLY-2608+fulvestrant+ribo600mg for HR+HER2- locally advanced metastatic breast cancer Ribociclib 600mg Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg 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 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 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 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 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 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
- 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 PK parameters including area under the plasma concentration vs time curve during a dose interval (AUC0-tau) of RLY-2608 (and its metabolites, as appropriate) administered with fulvestrant + palbociclib, or ribociclib, or PF-07220060 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 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 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 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 (37)
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of California-San Diego
🇺🇸San Diego, California, United States
HealthONE
🇺🇸Denver, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
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
Community Health Network
🇺🇸Indianapolis, Indiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Scroll for more (27 remaining)The University of Arizona Cancer Center🇺🇸Tucson, Arizona, United States