Phase III study of RLY-2608 + Fulvestrant compared to Capivasertib + Fulvestrant for the treatment of locally advanced or metastatic PIK3CA-mutated HR+/HER2- breast cancer
Summary description of the study
This study will be conducted with adult participants diagnosed with HR+/HER2- advanced or metastatic (spread to other body areas) breast cancer, whose cancer has progressed after treatment with a CDK4/6 inhibitor and hormone therapy, and whose tumor has a mutation in the PIK3CA gene. The main goal of this study is to investigate the efficacy of the study drug RLY-2608 in combination with Fulvestrant compared to Capivasertib plus Fulvestrant, measured by how long participants live without their cancer worsening. About 540 participants are expected for this study. All participants will be randomly assigned (like flipping a coin) to one of 2 groups and will receive either RLY-2608 + Fulvestrant or Capivasertib + Fulvestrant. The probability of being assigned to either group is equal for the participants. You and your doctor will know which treatment you are receiving.
(BASEC)
Intervention under investigation
All participants will be randomly assigned (like flipping a coin) to one of 2 groups and will receive either RLY-2608 + Fulvestrant or Capivasertib + Fulvestrant. The probability of being assigned to either group is equal for the participants. You and your doctor will know which treatment you are receiving.
Treatment will occur in 4-week or 28-day "treatment cycles." A treatment cycle is the period during which a treatment is administered.
RLY-2608 is taken orally twice a day with a meal.
Capivasertib is taken orally twice a day for 4 days regardless of meals, followed by a 3-day break. After each 3-day break, participants resume treatment.
Fulvestrant is administered as an intramuscular injection on Day 1 and Day 15 of Cycle 1 and then on Day 1 of each subsequent cycle.
Participants are expected to remain in the study generally until their cancer progresses (as seen on CT or MRI scans) or the participant begins a new cancer treatment, or until a clinically significant adverse event occurs that necessitates discontinuation of treatment, or until they are no longer able to complete required aspects of the study treatment, or until it is determined that discontinuation is in the best interest of the participant, such as in the event of pregnancy, or until they discontinue treatment.
(BASEC)
Disease under investigation
PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locally advanced or metastatic breast cancer
(BASEC)
1. The participant must have a confirmed diagnosis of advanced or metastatic breast cancer that has recurred or worsened. The cancer should not be treatable with surgery aimed at cure. The participant is not eligible for participation if they are considered suitable for surgery or other curative measures. 2. The participant must have a known PIK3CA mutation in tissue or blood confirmed by testing. If the central testing cannot confirm the mutation, individuals may still participate with the sponsor's consent and must provide tumor tissue for confirmation. 3. The participant must demonstrate that their cancer has worsened after prior treatment of HR+/HER2- advanced breast cancer, which included: - One or 2 lines of hormone therapy (HT) in early or advanced stages. This includes various types of HT, such as aromatase inhibitors, SERMs, and SERDs. - A prior therapy with CDK4/6 inhibitors either in advanced stage or in early stage if progression occurred within 12 months after completion of treatment. A switch of CDK4/6 inhibitors due to side effects is not considered a new line of therapy. (BASEC)
Exclusion criteria
1. Participants with Type 1 diabetes or Type 2 diabetes requiring specific medication, or with high blood sugar levels (≥ 140 mg/dl) or high HbA1c levels (≥ 7.0 %) 2. Participants who have previously been treated with certain inhibitors (CDK2, selective CDK4, PI3K, AKT, mTOR), immunotherapies, or antibody-drug conjugates) 3. Participants who have received more than 2 lines of hormone therapy for advanced breast cancer. Participants who responded to first-line HT within the first 6 months are excluded. The above inclusion and exclusion criteria are simplified for ease of understanding for participants. The original wording of the inclusion and exclusion criteria can be found in the study protocol. (BASEC)
Trial sites
Aarau, Basel
(BASEC)
Sponsor
Relay Therapeutics, Inc. Lumis International GmbH
(BASEC)
Contact
Contact Person Switzerland
Eunice Kwak, MD
+1 617-322-0731
ClinicalTrials@clutterrelaytx.comRelay Therapeutics, Inc.
(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
24.02.2026
(BASEC)
ICTRP Trial ID
not available
Official title (approved by ethics committee)
Eine offene, randomisierte Phase-III-Studie zur Beurteilung der Wirksamkeit und Sicherheit von RLY-2608 + Fulvestrant im Vergleich zu Capivasertib + Fulvestrant zur Behandlung von PIK3CA-mutiertem, Hormonrezeptor-positivem, humanen epidermalen Wachstumsfaktor-Rezeptor-2-negativen (HR+/HER2-) lokal fortgeschrittenen oder metastasierten Brustkrebs nach Rezidiv oder Progression während oder nach einer Behandlung mit einem CDK4/6-Inhibitor (BASEC)
Academic title
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Public title
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Disease under investigation
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Intervention under investigation
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Type of trial
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Trial design
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Inclusion/Exclusion criteria
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Primary and secondary end points
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Registration date
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Incorporation of the first participant
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Secondary sponsors
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Additional contacts
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Secondary trial IDs
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Results-Individual Participant Data (IPD)
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Further information on the trial
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Results of the trial
Results summary
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Link to the results in the primary register
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