First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other Solid Tumors
Phase 1
Completed
- Conditions
- HER2-negative Breast CancerBreast CancerUnresectable Solid TumorPIK3CA MutationSolid Tumor, AdultHormone Receptor Positive TumorMetastatic Breast CancerAdvanced Breast Cancer
- Interventions
- Registration Number
- NCT05759949
- Lead Sponsor
- Relay Therapeutics, Inc.
- Brief Summary
This is a Phase 1, first-in-human, open-label study designed to evaluate the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RLY-5836 in advanced solid tumors in participants harboring a PIK3CA mutation in blood and/or tumor per local assessment. The study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
Inclusion Criteria
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
RLY-5836 single agent arm key inclusion criteria
- Disease that is refractory to standard therapy, intolerant to standard therapy, or participant has declined standard therapy.
- A histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor
Combination arms key inclusion criteria
- Males, postmenopausal females, or pre-/perimenopausal females previously treated with gonadotropin-releasing GnRH agonist at least 4 weeks prior to start of study drug with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy.
- Had previous treatment for advanced or metastatic breast cancer with antiestrogen therapy including, but not limited to, selective estrogen receptor degraders (e.g., fulvestrant), selective estrogen receptor modulators (e.g., tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane)
- Part 1: Prior PI3Kα inhibitor treatment is allowed if taken for < 14 days and not discontinued due to disease progression, hypersensitivity, or ≥ Grade 3 TEAEs.
Exclusion Criteria
- Part 2: Prior treatment with PI3Kα inhibitors.
- Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RLY-5836 Single Agent Arm RLY-5836 RLY-5836 single agent arm for participants with unresectable or metastatic solid tumors RLY-5836 + Fulvestrant Arm Fulvestrant RLY-5836 + fulvestrant combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Palbociclib + Fulvestrant Arm RLY-5836 RLY-5836 + palbociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Palbociclib + Fulvestrant Arm Fulvestrant RLY-5836 + palbociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Palbociclib + Fulvestrant Arm Palbociclib RLY-5836 + palbociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Ribociclib + Fulvestrant Arm RLY-5836 RLY-5836 + ribociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Ribociclib + Fulvestrant Arm Fulvestrant RLY-5836 + ribociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Abemaciclib + Fulvestrant Arm RLY-5836 RLY-5836 + abemaciclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Abemaciclib + Fulvestrant Arm Abemaciclib RLY-5836 + abemaciclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Fulvestrant Arm RLY-5836 RLY-5836 + fulvestrant combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Ribociclib + Fulvestrant Arm Ribociclib RLY-5836 + ribociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer RLY-5836 + Abemaciclib + Fulvestrant Arm Fulvestrant RLY-5836 + abemaciclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of RLY-5836 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 participants with any dose-limiting toxicity (DLT) Cycle 1, up to 28 days. Number of participants with adverse events (AEs) Every cycle (4-week cycles) until study discontinuation, approximately 24 months Number of participants with serious adverse events (SAEs) Every cycle (4-week cycles) until study discontinuation, approximately 24 months
- Secondary Outcome Measures
Name Time Method PK of RLY-5836: maximum plasma concentration (Cmax) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months PK of RLY-5836: half-life (t½) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months Changes in circulating markers of glucose metabolism: changes in circulating glucose Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months Changes in circulating markers of glucose metabolism: changes in circulating C-peptide Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months Preliminary antitumor activity of RLY-5836: duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Approximately every 8 weeks until progressive disease, approximately 36 months Preliminary antitumor activity of RLY-5836: objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Approximately every 8 weeks until progressive disease, approximately 36 months PIK3CA genotype in blood and tumor tissue by next generation nucleic acid sequencing Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months PK of RLY-5836: area under the concentration-time curve (AUC) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months PK of RLY-5836: time to maximum concentration (tmax) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months PK of RLY-5836: clearance following oral dose (CL/F) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months Changes in circulating markers of glucose metabolism: changes in circulating insulin Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months Changes in circulating markers of glucose metabolism: changes in circulating glycosylated hemoglobin [HbA1c] Approximately every week in Cycle 1 (4-week cycle), every 2 weeks in Cycle 2 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months Preliminary antitumor activity of RLY-5836: disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Approximately every 8 weeks until progressive disease, approximately 36 months
Trial Locations
- Locations (7)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Community Cancer Center North
🇺🇸Indianapolis, Indiana, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center-Main Campus
🇺🇸New York, New York, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute at Florida Cancer Specialists
🇺🇸Orlando, Florida, United States