Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer

Launched by RELAY THERAPEUTICS, INC. · May 20, 2025

Keywords

ClinConnect Summary

This clinical trial is studying two different treatment combinations for patients with a specific type of breast cancer called HR+/HER2- that has a PIK3CA mutation. The researchers want to see how well RLY-2608 combined with fulvestrant works compared to another treatment, capivasertib combined with fulvestrant. This trial is for adults who have already experienced recurrence or progression of their cancer after receiving previous treatments, specifically targeting those who have had certain types of hormone therapies and a CDK4/6 inhibitor.

To be eligible for this trial, participants need to be adults with a confirmed diagnosis of locally advanced or metastatic breast cancer that has a PIK3CA mutation. They should have good overall health (an ECOG performance status of 0-1) and must have measurable disease. Women who are pre-menopausal can join if they are also receiving specific hormone therapy. Participants can expect to receive one of the two treatment combinations and will be closely monitored for safety and effectiveness throughout the study. It's important to note that people with certain health conditions or previous treatments that affect their eligibility will not be able to participate.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Patient has ECOG performance status of 0-1
• • One or more known primary oncogenic PIK3CA mutation(s)
• • 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.
• • 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
• • Measurable disease per RECIST v1.1 or evaluable bone-only disease.
• * Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with:
• • 1. At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting
• 2. 1 prior line of CDK4/6 inhibitor therapy in one of the following settings:
• • 1. CDK4/6 inhibitor + ET in the ABC setting
• • 2. CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET
• • 3. Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had \>1 prior line of CDK4/6 inhibitor and are not eligible
• Exclusion Criteria:
• * Prior treatment with any of the following:
• • 1. CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases
• • 2. PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
• • 3. Immunotherapy
• • 4. Antibody drug conjugates
• • Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL, or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
• • Clinically significant, uncontrolled cardiovascular disease
• • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
• • Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
• • 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
• • History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients
• • Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K