A Phase 3 Open-Label Randomized Study Assessing the Efficacy and Safety of RLY-2608 + Fulvestrant Versus Capivasertib + Fulvestrant as Treatment for PIK3CA-mutant Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Locally Advanced or Metastatic Breast Cancer Following Recurrence or Progression On or After Treatment With a CDK4/6 Inhibitor

Plain English Summary

Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer is a Phase 3 clinical trial sponsored by Relay Therapeutics, Inc. studying PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer. Tests RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant for treating PIK3CA-mutant HR+/HER2- breast cancer. For patients with advanced or metastatic breast cancer who have progressed after CDK4/6 inhibitor therapy. Participation involves taking study drugs and regular check-ups. Patients will be randomly assigned to one of the treatment groups. Alternative treatments include other targeted therapies and hormone therapies. The trial aims to enroll 540 participants.

Official Summary

This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if you have a PIK3CA mutation, HR+/HER2- breast cancer, and have progressed after CDK4/6 inhibitor therapy. Adult females and males are eligible. Pre-menopausal women may be included if they are treated with a GnRH agonist. Age 18 and older. Good overall health with no major health issues. Must not have had prior treatment with certain drugs or have specific health conditions like diabetes or cardiovascular disease. This trial is studying PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the time until the cancer progresses or the patient dies, helping to determine the effectiveness of the treatments. The specific primary outcome measures are: Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR) (The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a significant treatment gap for patients with PIK3CA-mutant HR+/HER2- breast cancer who have progressed after CDK4/6 inhibitor therapy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape indicate a high potential for approval and commercial success. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 540 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have a PIK3CA mutation and if you are a candidate for this trial. Participation involves taking study drugs daily and having regular check-ups at the clinic. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 540 participants

Interventions

• DRUG: RLY-2608 — 400 mg orally BID administered daily on a 28-day treatment cycle
• DRUG: Capivasertib — 400mg orally BID administered on an intermittent weekly dosing schedule. Patients will dose on Days 1 through 4 each week of a 28-day treatment cycle
• DRUG: Fulvestrant — 500 mg intramuscularly administered on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (28-day treatment cycle)

Primary Outcomes

• Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR) (The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months)

Secondary Outcomes

• Overall Survival (OS) within the overall and kinase populations (The time from randomization to the date of death by any cause, up to approximately 77 months)
• PFS by Investigator within the overall and kinase populations (The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months)
• Objective Response Rate (ORR) within the overall and kinase populations (Up to approximately 77 months)
• Duration of Response (DOR) within the overall and kinase populations (Up to approximately 77 months)
• Clinical Benefit Rate (CBR) within the overall and kinase populations (Up to approximately 77 months)

Full 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

Trial Locations

• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• Beverly Hills Cancer Center, Beverly Hills, California, United States
• Cedars-Sinai Medical Center, Beverly Hills, California, United States
• City of Hope, Duarte, California, United States
• Stanford University School of Medicine, Palo Alto, California, United States
• University of California Davis, Sacramento, California, United States
• University of California San Diego, San Diego, California, United States
• University of California San Francisco, San Francisco, California, United States
• Kaiser Permanente - Vallejo, Vallejo, California, United States
• Rocky Mountain Cancer Centers, Longmont, Colorado, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast cancer, PIK3CA mutation, HR+/HER2- breast cancer, advanced breast cancer, metastatic breast cancer

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