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

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).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Advanced Breast Cancer; Metastatic Breast Cancer; Solid Tumor, Adult; HER2-negative Breast Cancer; Unresectable Solid Tumor; PIK3CA Mutation
• Intervention / Treatment: Drug: RLY-2608; Drug: Fulvestrant; Drug: Palbociclib 125mg; Drug: Ribociclib 400mg; Drug: Ribociclib 600mg; Drug: PF-07220060 100mg; Drug: PF-07220060 300 mg

• Study Type: Interventional
• Enrollment (Estimated): 930
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Relay Therapeutics Inc; Phone Number: 617-322-0731; Email: ClinicalTrials@relaytx.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2019
      • Recruiting
      • St Vincents Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Center
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Institute Bergonié
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France, 69008
      • Recruiting
      • Centre Léon Bérard
• Italy
  • Milan, Italy, 20141
    • Recruiting
    • Istituto Europeo di Oncologia IRCCS
• Spain
  • Barcelona, Spain, 08916
    • Recruiting
    • Institut Catala D'Oncologia - Badalona (ICO Badalona)
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • START Madrid - Hospital Fundacion Jimenez Diaz
  • Barcelona
    • Barcelona, Barcelona, Spain, 08035
      • Recruiting
      • Vall d'Hebron Instituto de Oncologia
  • Catalonia
    • Barcelona, Catalonia, Spain, 08023
      • Recruiting
      • Start Barcelona
  • Valencia
    • Valencia, Valencia, Spain, 46009
      • Recruiting
      • Instituto Valenciano de Oncologia
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • The University of Arizona Cancer Center
  • California
    • San Diego, California, United States, 90293
      • Recruiting
      • University of California-San Diego
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • HealthONE
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University
  • Florida
    • Orlando, Florida, United States, 32827
      • Recruiting
      • Florida Cancer Specialists
    • Plantation, Florida, United States, 33322
      • Withdrawn
      • Boca Raton Clinical Research (BRCR) Global
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Community Health Network
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine St. Louis
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Renown Regional Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers University
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Herbert Irving Comprehensive Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas M.D. Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah- Huntsman Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22301
      • Recruiting
      • Next Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Inova Schar Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • UW Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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

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

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

Key Inclusion for RLY-2608 Single Agent Arm

• [For Part 1: Escalation]: Evaluable disease per RECIST v1.1
• [For Part 2: Expansion]: Measurable disease per RECIST v1.1
• 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 In addition, the SRC (with Sponsor approval) may choose to open additional group(s) of 20 participants to study the clinical activity, safety, and PK/PD with other specified solid tumor types.

Key Inclusion for Combination Arms:

• Doublet combination arms [Part 1 and Part 2]: Evaluable disease per RECIST v1.1
• Triplet combination arms:
• [Part 1 and Part 2 Dose Expansion, Group 1]: Evaluable disease per RECIST.
• [Part 2 Dose Expansion, Group 2]: Measurable disease per RECIST. Bone-only lytic or lytic/blastic disease with at least 1 measurable soft-tissue component per RECIST may be eligible.
• [For Part 1 and Part 2]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy and must have initiated treatment with a gonadotropin-releasing hormone (GnRH) agonist at least 4 weeks prior to start of study drug with continuation of GnRH agonist for the duration of study treatment (GnRH agonist recommended for males).

• Had previous treatment for breast cancer with: [Does not apply to triplet combination arms, Part 2 Dose Expansion, Group 2]:

  1. ≤1 line of chemotherapy in the metastatic setting
  2. ≥1 CDK4/6 inhibitor in either the adjuvant and/or metastatic setting
  3. ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
  4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment

[For double combination arm; Part 2 Dose Expansion, Group 2]: Received prior treatment with a PI3Kα, AKT, or mTOR 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.

[For triple combination arms; Part 1 dose escalation]: Participants who had previous treatment for breast cancer with PI3Kα, AKT, mTOR inhibitors and discontiuned due to participant/physician decision, intolerance, or disease progression will be considered.

[For triple combination arms, Part 2 Dose Expansion, Group 2]: Participants must be intolerant to or have declined standard therapy for locally advanced or metastatic HR+/HER2- PIK3CA-mutated breast cancer. Prior endocrine therapy and CDK4/6inhibitors are allowed as follows:

1. Participants must have progressed during (neo)adjuvant endocrine therapy or within12 months of completing (neo)adjuvant endocrine therapy with an AI or tamoxifen.
2. If a CDK4/6 inhibitor was included as part of (neo)adjuvant therapy, disease must have recurred/progressed >12 months after completion of the CDK4/6 inhibitor portion of (neo)adjuvant therapy

Key Exclusion Criteria

Prior treatment with:

1. PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation).
2. Immune checkpoint inhibitors.
3. Triplet combinations RLY-2608 + CDK4 or CDK4/6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only:

i. Prior systemic chemotherapy or antibody drug conjugate for locally advanced or metastatic disease. ii. Prior CDK2, CDK4, or CDK4/6 inhibitor as treatment for locally advanced or metastatic disease.

iii. Prior treatment with fulvestrant or any selective ER degrader, with the exception of patients who have received fulvestrant or any selective ER degrader as part of neoadjuvant therapy only and with treatment duration ≤6 months.

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

History of allergy or hypersensitivity to any components or excipients of PI3K inhibitors. For combination arms only: allergy or hypersensitivity to any components or excipients of fulvestrant, palbociclib, ribociclib, and/or PF-07220060 as appropriate for the combination.

Past medical history of or ongoing ILD, or pneumonitis requiring intervention. Participants with past history of resolved Grade 1 pneumonitis may be considered, except in triple combination arms.

The following cardiac criteria:

• Mean resting corrected QT interval (QTc) >460 msec
• For triple combination arm with ribociclib: Mean QTcF ≥450 msec (this is what we confirmed is shown in the redacted version of the protocol.

CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / 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; 500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).; Other Names: Faslodex
Experimental: RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancer; Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation	Drug: RLY-2608; RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.; Drug: Fulvestrant; 500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).; Other Names: Faslodex; Drug: PF-07220060 100mg; PF-07220060 100 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
Experimental: RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancer; Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation	Drug: RLY-2608; RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.; Drug: Fulvestrant; 500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).; Other Names: Faslodex; Drug: PF-07220060 300 mg; PF-07220060 300 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
Experimental: RLY-2608+fulvestrant+palbo125mg for HR+HER2- locally advanced metastatic breast cancer; Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation.	Drug: RLY-2608; RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.; Drug: Fulvestrant; 500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).; Other Names: Faslodex; Drug: Palbociclib 125mg; 125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.; Other Names: Ibrance
Experimental: RLY-2608+fulvestrant+ribo400mg for HR+HER2- locally advanced metastatic breast cancer; Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation.	Drug: RLY-2608; RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.; Drug: Fulvestrant; 500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).; Other Names: Faslodex; Drug: Ribociclib 400mg; 400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.; Other Names: Kisqali
Experimental: RLY-2608+fulvestrant+ribo600mg for HR+HER2- locally advanced metastatic breast cancer; Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation.	Drug: RLY-2608; RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.; Drug: Fulvestrant; 500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).; Other Names: Faslodex; Drug: Ribociclib 600mg; 600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.; Other Names: Kisqali

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Every cycle (4-week cycles) until study discontinuation, approximately 24 months
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 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

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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 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
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
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
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 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
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
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]
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 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
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

Collaborators and Investigators

• Sponsor: Relay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; ribociclib; palbociclib
• Other Study ID Numbers: RLY-2608-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No