RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant for Breast Cancer

(ReDiscover-2 Trial)

Recruiting at 25 trial locations

Overseen By Relay Therapeutics, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Relay Therapeutics, Inc.

Must be taking: GnRH agonists

Must not be taking: Immunotherapy, Antibody drug conjugates

Disqualifiers: Diabetes, Cardiovascular disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

540 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two different treatment combinations for individuals with advanced breast cancer that is hormone receptor-positive, HER2-negative, and has a specific gene mutation called PIK3CA. The goal is to determine which combination—RLY-2608 (an experimental treatment) with fulvestrant or capivasertib with fulvestrant—proves more effective and safer for patients whose cancer has progressed after certain previous treatments. Suitable candidates have this specific type of breast cancer and have already tried treatments like a CDK4/6 inhibitor without success. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially effective treatments.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain diabetes medications or treatments targeting specific cancer pathways, you may not be eligible. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of RLY-2608 and fulvestrant is generally safe for patients with advanced breast cancer. Patients have tolerated the treatment well, and it appears safe for various genetic types of the cancer. So far, no major safety issues have emerged.

For capivasertib plus fulvestrant, studies indicate that this combination is already recommended for certain breast cancers. It is approved for patients with hormone receptor-positive, HER2-negative advanced breast cancer. This suggests the treatment is generally considered safe, with no serious safety problems identified in these studies.

Both treatments have undergone testing in earlier studies, which helps ensure their safety for patients considering participation in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RLY-2608 combined with fulvestrant because RLY-2608 is a novel inhibitor that targets the PI3K-alpha pathway, which plays a key role in cancer cell growth and survival, especially in HR+/HER2- advanced breast cancer. Unlike current treatments that primarily focus on hormone receptors, RLY-2608 provides a targeted approach that may overcome resistance seen with other therapies. Meanwhile, the combination of capivasertib with fulvestrant offers a different mechanism by inhibiting the AKT pathway, which is also crucial for cancer cell proliferation. These innovative approaches could offer new hope for patients by potentially improving outcomes and expanding treatment options beyond traditional hormonal therapies.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare two treatment combinations for HR+/HER2- advanced breast cancer: RLY-2608 with fulvestrant and capivasertib with fulvestrant. Research has shown that the combination of RLY-2608 and fulvestrant is promising for treating advanced breast cancer with a PIK3CA mutation that is hormone receptor-positive but HER2-negative. In earlier studies, patients lived for an average of 11 months without cancer progression, suggesting that the treatment might slow the cancer's progression.

Similarly, the combination of capivasertib and fulvestrant, which participants in another arm of this trial may receive, has also proven effective. Studies found that this combination reduces the risk of cancer worsening or causing death by 40% compared to fulvestrant alone. Additionally, 40% of patients with PIK3CA-mutated breast cancer experienced tumor shrinkage. Both treatment combinations show potential, each with different strengths in patient outcomes. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with HR+/HER2- advanced breast cancer that has a PIK3CA mutation and worsened after CDK4/6 inhibitor treatment. Participants must have an ECOG performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Pre-menopausal women must agree to hormone suppression therapy.

Inclusion Criteria

* Measurable disease per RECIST v1.1 or evaluable bone-only disease.

My breast cancer is advanced, cannot be surgically removed, and is worsening.

I have been treated with CDK4/6 inhibitors and hormone therapy for advanced breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either RLY-2608 + fulvestrant or capivasertib + fulvestrant for HR+/HER2- advanced breast cancer

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capivasertib
• RLY-2608

Trial Overview The study compares RLY-2608 combined with fulvestrant against capivasertib plus fulvestrant in treating advanced breast cancer with the PIK3CA mutation. It's a global Phase 3 trial where patients are randomly assigned to either treatment group.

How Is the Trial Designed?

Group I: RLY-2608 + fulvestrant Experimental Treatment 2 Interventions

RLY-2608 + fulvestrant combination for participants with HR+/HER2- advanced breast cancer

Group II: capivasertib + fulvestrant Active Control 2 Interventions

capivasertib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer

Who Is Running the Clinical Trial?

Relay Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

1,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12317260/

Capivasertib/Fulvestrant in patients with HR+, HER2-low or ... Forty percent of patients in the PIK3CA-mutated breast cancer cohort achieved a reduction in tumour size, with a further 4% of patients ...

2. nature.com nature.com/articles/s41467-025-59210-6

Capivasertib plus fulvestrant in patients with HR-positive/ ... Overall, 10 patients (14.1%) receiving capivasertib–fulvestrant and 16 patients (25.4%) receiving placebo–fulvestrant had died. Median overall ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214131

Capivasertib in Hormone Receptor–Positive Advanced ... Capivasertib–fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients ...

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2025.31.9.900

Capivasertib cost-effectiveness in treating advanced breast ... This study found that adding capivasertib to fulvestrant is not cost-effective compared with fulvestrant alone for patients with advanced breast ...

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2022/capivasertib-plus-faslodex-fulvestrant-reduced-the-risk-of-disease-progression-or-death-by-40-versus-faslodex-in-advanced-hr-positive-breast-cancer-12082022.html

Capivasertib plus FASLODEX® (fulvestrant) reduced the ... Results showed capivasertib in combination with FASLODEX demonstrated a 40% reduction in the risk of disease progression or death versus placebo plus FASLODEX.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06764186

NCT06764186 | A Phase IIIB Study to Evaluate the Use of ... The purpose of this study is to evaluate the effectiveness and safety of capivasertib + fulvestrant treatment administration in patients with locally advanced ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK615830

Capivasertib with fulvestrant for treating hormone receptor ... Capivasertib plus fulvestrant is recommended as an option for treating hormone receptor (HR)-positive HER2-negative (defined as ...

8. esmoopen.com esmoopen.com/article/S2059-7029(24)01466-2/fulltext

Capivasertib and fulvestrant for patients with hormone ... These data led to the first regulatory approval of capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast ...