Clinical trial NCT05759949: First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other Solid Tumors
Official title: A First-in-Human Study of PI3Kα Inhibitor, RLY-5836, in Combination With Targeted and Endocrine Therapies in Participants With Advanced Breast Cancer and as a Single Agent in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: PIK3CA Mutation
Solid Tumor, Adult
HER2-negative Breast Cancer
Breast Cancer
Metastatic Breast Cancer
Advanced Breast Cancer
Unresectable Solid Tumor
Hormone Receptor Positive Tumor
Lead sponsor: Relay Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-08
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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%.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of RLY-5836
timeFrame: 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
measure: Number of participants with any dose-limiting toxicity (DLT)
timeFrame: Cycle 1, up to 28 days.
measure: Number of participants with adverse events (AEs)
timeFrame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Secondary outcomes:
measure: PIK3CA genotype in blood and tumor tissue by next generation nucleic acid sequencing
timeFrame: Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months
measure: PK of RLY-5836: area under the concentration-time curve (AUC)
timeFrame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
measure: PK of RLY-5836: maximum plasma concentration (Cmax)
timeFrame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
measure: PK of RLY-5836: time to maximum concentration (tmax)
timeFrame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
measure: PK of RLY-5836: half-life (t½)
timeFrame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
measure: PK of RLY-5836: clearance following oral dose (CL/F)
timeFrame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment (4-week cycles), approximately 24 months
measure: Changes in circulating markers of glucose metabolism: changes in circulating glucose
timeFrame: 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
measure: Changes in circulating markers of glucose metabolism: changes in circulating insulin
timeFrame: 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
measure: Changes in circulating markers of glucose metabolism: changes in circulating C-peptide
timeFrame: 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
measure: Changes in circulating markers of glucose metabolism: changes in circulating glycosylated hemoglobin [HbA1c]
timeFrame: 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
measure: Preliminary antitumor activity of RLY-5836: duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
timeFrame: Approximately every 8 weeks until progressive disease, approximately 36 months
measure: Preliminary antitumor activity of RLY-5836: disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
timeFrame: Approximately every 8 weeks until progressive disease, approximately 36 months
measure: Preliminary antitumor activity of RLY-5836: objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
timeFrame: Approximately every 8 weeks until progressive disease, approximately 36 months
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Indianapolis
country: United States
facility: Community Cancer Center North
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Main Campus
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
Study officials:
References: