First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other Solid Tumors

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05759949
• Other study ID #: RLY-5836-101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 29, 2023
• Est. completion date: July 25, 2024

Study information

• Verified date: February 2024
• Source: Relay Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 265
• Est. completion date: July 25, 2024
• Est. primary completion date: June 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PI3Ka 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 PI3Ka inhibitors.
• Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose =140 mg/dL and glycosylated hemoglobin (HbA1c) =7.0%.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Neoplasms
• HER2-negative Breast Cancer
• Hormone Receptor Positive Tumor
• Metastatic Breast Cancer
• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• RLY-5836
RLY-5836 is a mutant-selective, oral PI3Ka inhibitor.
• Fulvestrant
Fulvestrant (500 mg) is administered IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as 2×5 mL injections, 1 in each buttock, on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of each subsequent cycle.
• Palbociclib
Palbociclib 125 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
• Ribociclib
Ribociclib 600 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
• Abemaciclib
Abemaciclib 150 mg BID will be taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
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	Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Relay Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with any dose-limiting toxicity (DLT)		Cycle 1, up to 28 days.
Primary	Number of participants with adverse events (AEs)		Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Primary	Number of participants with serious adverse events (SAEs)		Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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