Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 60 for:    relay therapeutics
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05216432
Recruitment Status : Recruiting
First Posted : January 31, 2022
Last Update Posted : February 18, 2022
Sponsor:
Information provided by (Responsible Party):
Relay Therapeutics, Inc.

Brief Summary:
This is an open-label, FIH study designed to evaluate the maximum tolerated 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 both RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors and RLY-2608 + fulvestrant combination arm for patients with HR+ HER2- locally advanced or metastatic breast cancer. This study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).

Condition or disease Intervention/treatment Phase
PIK3CA Mutation Solid Tumor, Adult HER2-negative Breast Cancer Breast Cancer Metastatic Breast Cancer Advanced Breast Cancer Unresectable Solid Tumor Drug: RLY-2608 Drug: Fulvestrant Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

RLY-2608 Single Agent Arm:

Part 1(multiple ascending doses, QD or BID):unresectable or metastatic solid tumors with PIK3CA mutation per local assessment; Part 2 (RP2D determined in Part 1) Patients with the following unresectable or metastatic solid tumors with ≥1 PIK3CA mutation per local assessment will be enrolled protocol defined groups

RLY-2608+Fulvestrant Arm Part 1(multiple ascending doses, QD or BID): HR+, HER2- advanced or metastatic breast cancer with PIK3CA mutation per local assessment Part 2 (RP2D determined in Part 1)

  • Group 1: patients who have not received prior PI3Kα inhibitor
  • Group 2: patient who are intolerant to PI3Kα inhibitor
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 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
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : August 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Experimental: RLY-2608 for patients with unresectable or metastatic solid tumors
Multiple doses of RLY-2608 for oral administration.
Drug: RLY-2608
RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Experimental: RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancer
Oral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation.
Drug: RLY-2608
RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Drug: Fulvestrant
Fulvestrant is a nonmutant selective PI3K inhibitor
Other Name: Alpelisib




Primary Outcome Measures :
  1. Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-2608 as a single agent [ Time Frame: 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 recommended Phase 2 dose (RP2D) of RLY-2608 as a single agent

  2. Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant [ Time Frame: 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 recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant

  3. Number of patients with adverse events and serious adverse events of RLY-2608 as a single agent [ Time Frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months ]
    Number of patients with adverse events and serious adverse events of RLY-2608 as a single agent

  4. Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant [ Time Frame: 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


Secondary Outcome Measures :
  1. PIK3CA gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue [ Time Frame: Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months ]
    PIK3CA gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue

  2. Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) as single agent [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
    Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) as single agent

  3. Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24) of RLY-2608 (and its metabolites, as appropriate) as single agent [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
    Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24) of RLY-2608 (and its metabolites, as appropriate) as single agent

  4. Pharmacokinetic parameters including terminal elimination half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) as single agent [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
    Pharmacokinetic parameters including terminal elimination half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) as single agent

  5. 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 [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
    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

  6. Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
    Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant

  7. Pharmacokinetic parameters including terminal elimination half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
    Pharmacokinetic parameters including terminal elimination half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant

  8. Changes in circulating blood of fasting glucose in RLY-2608 as a single agent [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Changes in circulating blood of fasting glucose in RLY-2608 as a single agent

  9. Changes in circulating blood of insulin in RLY-2608 as a single agent [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Changes in circulating blood of insulin in RLY-2608 as a single agent

  10. Changes in circulating blood of C-peptide in RLY-2608 as a single agent [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Changes in circulating blood of C-peptide in RLY-2608 as a single agent

  11. Changes in circulating blood of fasting glucose in RLY-2608 in combination with fulvestrant [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Changes in circulating blood of fasting glucose in RLY-2608 in combination with fulvestrant

  12. Changes in circulating blood of insulin in RLY-2608 in combination with fulvestrant [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Changes in circulating blood of insulin in RLY-2608 in combination with fulvestrant

  13. Changes in circulating blood of C-peptide in RLY-2608 in combination with fulvestrant [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Changes in circulating blood of C-peptide in RLY-2608 in combination with fulvestrant

  14. Pharmacodynamic parameters including changes in PI3Kα signaling [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
    Pharmacodynamic parameters including changes in PI3Kα signaling

  15. Overall response rate (ORR) 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 ]
    Overall response rate (ORR) as assessed by RECIST v1.1

  16. Duration of Response (DOR) 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 ]
    Duration of Response (DOR) as assessed by RECIST v1.1

  17. Disease Control Rate (DCR) 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 ]
    Disease Control Rate (DCR) as assessed by RECIST v1.1



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria

Part 1- Evaluable disease per RECIST Version 1.1 Part 2 - Measurable disease per RECIST Version 1.1

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

- Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment.

Part 1 - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively.

Key Inclusion for RLY-2608 Single Agent Arm

- Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy. Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor

Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types:

Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations

Key Inclusion for RLY-2608 + Fulvestrant Arm

- Male or postmenopausal female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative therapy and must have been previously treated with GnRH agonist at least 4 weeks prior to start of study drug

[ For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast cancer with:

  1. ≤1 chemotherapy regimen,
  2. ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and
  3. ≥1 antiestrogen therapy including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane)

[For Part 2, Group 2]: Received prior treatment with a PI3Kα inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.

Key Exclusion Criteria

Prior treatment with PI3Kα inhibitors (except for RLY-2608 + fulvestrant arm, Part 2, Group 2).

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

History of hypersensitivity to PI3K inhibitors

QT interval corrected using Fridericia's formula (QTcF) > 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05216432


Contacts
Layout table for location contacts
Contact: Relay Therapeutics Inc 617-322-0731 ClinicalTrials@relaytx.com

Locations
Layout table for location information
United States, Colorado
HealthONE Recruiting
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists Recruiting
Orlando, Florida, United States, 32827
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Virginia
NEXT Virginia Recruiting
Fairfax, Virginia, United States, 22301
Sponsors and Collaborators
Relay Therapeutics, Inc.
Layout table for additonal information
Responsible Party: Relay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05216432    
Other Study ID Numbers: RLY-2608-101
First Posted: January 31, 2022    Key Record Dates
Last Update Posted: February 18, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs