RLY-2608 for PIK3CA-mutated hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Patient has ECOG performance status of 0-1\n- Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 4 weeks prior to randomization and must be willing to continue on it for the duration of the study.\n- Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent\n- Measurable disease per RECIST v1.1 or evaluable bone-only disease.\n- One or more known primary oncogenic PIK3CA mutation(s)\n- Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with: CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway Immunotherapy Antibody drug conjugates"}

Exclusion criteria

• {"criterion_text":"- History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients\n- Prior treatment with any of the following: CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway Immunotherapy Antibody drug conjugates\n- Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K\n- Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).\n- Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control\n- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\n- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events\n- Clinically significant, uncontrolled cardiovascular disease"}

Primary endpoints

• {"endpoint_text":"- PFS is defined as the time from randomization until radiographic progression per RECIST v1.1, or death due to any cause.","definition_or_measurement_approach":"PFS is defined as the time from randomization until radiographic progression per RECIST v1.1, or death due to any cause (assessed by BICR)."}

Secondary endpoints

• {"endpoint_text":"- OS is defined as the time from randomization to the date of death by any cause.","definition_or_measurement_approach":"Overall survival (OS) measured from randomization to date of death from any cause."}
• {"endpoint_text":"- PFS is defined as the time from randomization until radiographic progression per RECIST v1.1, or death due to any cause.","definition_or_measurement_approach":"Progression-free survival (PFS) assessed as time from randomization to radiographic progression per RECIST v1.1 or death (Investigator-assessed and BICR)."}
• {"endpoint_text":"- ORR is defined as the percentage of participants with CR or PR per RECIST v1.1.","definition_or_measurement_approach":"Objective response rate (ORR) = % participants with complete response (CR) or partial response (PR) per RECIST v1.1 (assessed by BICR and by Investigator)."}
• {"endpoint_text":"- DOR is defined as the time from the date of first documented response per RECIST v1.1 until date of documented progression or death in the absence of disease progression.","definition_or_measurement_approach":"Duration of response (DOR) measured from first documented response per RECIST v1.1 until documented progression or death in absence of progression."}
• {"endpoint_text":"- CBR is defined as the percentage of participants who achieved CR or PR at any time or SD maintained for ≥24 weeks per RECIST v1.1 (without subsequent therapy) after randomization.","definition_or_measurement_approach":"Clinical benefit rate (CBR) = % participants with CR or PR at any time or stable disease (SD) maintained ≥24 weeks per RECIST v1.1 after randomization (no subsequent therapy)."}
• {"endpoint_text":"- •\tFrequency, severity, timing, and relationship to RLY-2608/fulvestrant or capivasertib/fulvestrant of any AEs, SAEs, changes in vital signs, ECGs, and safety laboratory tests. All AEs and SAEs will be collected and graded according to the NCI CTCAE, Version 5.0. •\tDose intensity. • Dose modification.","definition_or_measurement_approach":"Safety and tolerability: collection of AEs/SAEs, vital signs, ECGs, safety labs; grading per NCI CTCAE v5.0; dose intensity and dose modifications tracked."}
• {"endpoint_text":"- Plasma concentrations of RLY-2608 (and its metabolites as appropriate).","definition_or_measurement_approach":"Pharmacokinetics: plasma concentrations of RLY-2608 and metabolites measured over defined PK sampling schedule."}
• {"endpoint_text":"- Evaluation of EORTC QLQ-C30, EORTC QLQ-BR23 scale/item scores including change from baseline and time to deterioration.","definition_or_measurement_approach":"Patient-reported outcomes: EORTC QLQ-C30 and QLQ-BR23 scores, change from baseline and time to deterioration."}
• {"endpoint_text":"- Health state utility data for economic evaluation will be derived by using the EQ-5D-5L health state utility index.","definition_or_measurement_approach":"Health state utility: EQ-5D-5L index used to derive utilities for economic evaluation."}

Methods

• Patient Invite-to-Trial Letter (documented - 'Patient Invite-to-Trial Letter') — invitation letters to potential participants (documents present in multiple countries).
• Recruitment Brochure — printed/electronic brochure for potential participants.
• Study Fact Sheet — brief study information for potential participants and sites.
• Thank You Card (for potential participants and caregivers) — post-contact acknowledgement materials.
• K1 recruitment arrangements and consent documents — site-level recruitment arrangements and consent materials (site-based recruitment).
• GP Letter — letters to general practitioners (present in other-subject information materials) to notify/referral.

Austria

Earliest CTIS Part Ii Submission Date

30-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

18

Number Of Sites

4

Number Of Participants

10

Belgium

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

168

Number Of Sites

12

Number Of Participants

20

Bulgaria

Earliest CTIS Part Ii Submission Date

02-10-2025

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

42

Number Of Sites

4

Number Of Participants

21

Czechia

Earliest CTIS Part Ii Submission Date

14-10-2025

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

30

Number Of Sites

8

Number Of Participants

11

Denmark

Earliest CTIS Part Ii Submission Date

21-10-2025

Latest Decision Or Authorization Date

11-11-2025

Processing Time Days

21

Number Of Sites

3

Number Of Participants

9

France

Earliest CTIS Part Ii Submission Date

27-10-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

164

Number Of Sites

32

Number Of Participants

32

Germany

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

203

Number Of Sites

11

Number Of Participants

23

Greece

Earliest CTIS Part Ii Submission Date

04-08-2025

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

235

Number Of Sites

7

Number Of Participants

10

Hungary

Earliest CTIS Part Ii Submission Date

03-10-2025

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

40

Number Of Sites

2

Number Of Participants

13

Italy

Earliest CTIS Part Ii Submission Date

07-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

41

Number Of Sites

16

Number Of Participants

32

Portugal

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

11-11-2025

Processing Time Days

60

Number Of Sites

4

Number Of Participants

14

Spain

Earliest CTIS Part Ii Submission Date

28-10-2025

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

15

Number Of Sites

26

Number Of Participants

42

Netherlands

Earliest CTIS Part Ii Submission Date

24-10-2025

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

20

Number Of Sites

4

Number Of Participants

12

Poland

Earliest CTIS Part Ii Submission Date

27-10-2025

Latest Decision Or Authorization Date

15-11-2025

Processing Time Days

19

Number Of Sites

10

Number Of Participants

23

Primary sponsor

Full Name

Relay Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA RDS Hellas Single Member S.A.; IQVIA Limited; Iqvia Biotech LLC

Responsibilities

clinical operations / data management / other CRO services (sponsorDuties codes include 1,12,14,2,5,6 depending on entity)

Name

4g Clinical LLC

Responsibilities

clinical services (sponsorDuties code: 3)

Name

PCI Pharma Services Germany GmbH

Responsibilities

supply/logistics (sponsorDuties code: 14)

Third parties

• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"patient reimbursement support","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"codes: 1, 12, 2","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"codes: 13, 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"codes: 1, 12, 14, 2, 5, 6","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Clinical Logistics Inc.","duties_or_roles":"codes: 13, 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Biotec Services International Limited","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"codes: 13, 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: 6, 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Resolian Bioanalytics","duties_or_roles":"codes: 4","organisation_type":"Industry"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"codes: 13, 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clario Medical Imaging Inc.","duties_or_roles":"codes: 13, 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"codes: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Docs24 Limited","duties_or_roles":"site binders and CRF data distribution to sites at EOS (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Imaging Endpoints II LLC","duties_or_roles":"codes: 13, 7","organisation_type":"Pharmaceutical company"}