RLY-2608 plus fulvestrant versus capivasertib plus fulvestrant for PIK3CA‑mutant HR+/HER2‑ advanced breast cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a global, multicenter, open‑label, randomized Phase 3 trial comparing RLY-2608 plus fulvestrant against capivasertib plus fulvestrant in patients with HR+/HER2‑ locally advanced or metastatic breast cancer harboring PIK3CA mutations who have progressed after CDK4/6 inhibitor therapy. Eligible participants must have measurable disease or evaluable bone‑only disease and an ECOG performance status of 0–1, and premenopausal women must receive a GnRH agonist. Patients are randomized to one of the two combination regimens and undergo regular radiologic assessments per RECIST v1.1 with ongoing safety monitoring. The study is open‑label, so treating physicians and patients know the assigned therapy while outcomes are compared across the randomized arms.

Why it matters

Who can join: the full rules

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 2 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. Only 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 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor
  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 (7.8 mmol/L), 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, zovegalisib, 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

Where it's running

• Banner MD Anderson Cancer Center
  Gilbert, Arizona, United States Recruiting
• Beverly Hills Cancer Center
  Beverly Hills, California, United States Recruiting
• City of Hope National Medical Center
  Duarte, California, United States Recruiting
• Cedars-Sinai Medical Center
  Los Angeles, California, United States Recruiting
• Stanford Women's Cancer Center
  Palo Alto, California, United States Recruiting
• University of California, Davis Comprehensive Cancer Center
  Sacramento, California, United States Recruiting

+204 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Relay Therapeutics, Inc
• Email: ClinicalTrials@relaytx.com
• Phone: 617-322-0731

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Testing a new drug for advanced solid tumors and breast cancer with specific mutations

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.