RLY-5836 for Advanced Breast Cancer

No longer recruiting at 6 trial locations

Overseen By Relay Therapeutics Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Relay Therapeutics, Inc.

Must be taking: GnRH agonists

Must not be taking: PI3Kα inhibitors

Disqualifiers: Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called RLY-5836 for individuals with advanced breast cancer, specifically those with a PIK3CA mutation, which can affect cancer growth. The trial aims to determine the best dose and assess its safety and effectiveness, either alone or combined with medications like fulvestrant, palbociclib, ribociclib, and abemaciclib. Suitable candidates have HR+, HER2- breast cancer that has spread and have previously tried other hormone therapies. The trial seeks participants whose cancer has not responded to standard treatments or who cannot undergo surgery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have diabetes requiring medication, you may not be eligible to participate.

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

Research shows that RLY-5836 is being tested for safety in patients with advanced breast cancer. This trial is in its early stages, so detailed safety information for RLY-5836 alone is not yet available. However, similar drugs have shown promise in targeting specific cancer mutations.

Regarding combination treatments, Fulvestrant, used in some parts of the study, is generally well-tolerated and effective for advanced breast cancer. Previous studies have shown that Palbociclib and Ribociclib, both used with Fulvestrant in different combinations, are safe and well-tolerated for hormone receptor-positive breast cancer. Abemaciclib, another drug used in the study, is also approved for similar conditions and is usually well-tolerated.

Overall, while the safety of RLY-5836 alone is still under investigation, the combination treatments in the study involve drugs generally considered safe for similar patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the RLY-5836 treatments because they offer a fresh approach to tackling advanced breast cancer. Unlike standard therapies like hormone treatments and CDK4/6 inhibitors, RLY-5836 may provide a novel mechanism of action, potentially offering new hope for patients with hormone receptor-positive, HER2-negative breast cancer. The study includes multiple treatment combinations, such as RLY-5836 with fulvestrant, and triple combinations with palbociclib, ribociclib, or abemaciclib. These innovative pairings could enhance effectiveness and overcome resistance seen in current treatments. This new approach aims to improve outcomes for patients who have limited options with existing therapies.

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

In this trial, researchers will assign participants to different treatment arms to evaluate the effectiveness of RLY-5836 in advanced breast cancer. RLY-5836 has shown promise in research by targeting specific cancer cells. Although direct data on RLY-5836 alone is limited, similar treatments like fulvestrant have succeeded in this area. Some participants will receive RLY-5836 combined with fulvestrant, which studies suggest can help patients live longer without their cancer worsening. Other participants will receive combinations that include additional drugs like palbociclib, ribociclib, or abemaciclib, which have further improved results in similar conditions. Researchers are exploring these combinations to potentially achieve better outcomes for patients with advanced breast cancer. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced breast cancer or other solid tumors that have a PIK3CA mutation. Participants should be in good physical condition (ECOG 0-1), and women must be postmenopausal, treated with GnRH agonists, or otherwise not of childbearing potential. They should have tried standard treatments without success or cannot tolerate them.

Inclusion Criteria

I have HR+ and HER2- advanced breast cancer and cannot undergo surgery to cure it.

I am fully active or can carry out light work.

My condition hasn't improved with standard treatments, or I can't tolerate them.

Exclusion Criteria

I have diabetes and take medication, or my blood sugar and HbA1c levels are high.

I have previously been treated with PI3Kα inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive RLY-5836 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)

8-12 weeks

Dose Expansion

Participants receive RLY-5836 in combination with other therapies to evaluate safety, tolerability, and preliminary anti-tumor activity

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RLY-5836

Trial Overview RLY-5836 is being tested to find the safest and most effective dose for treating advanced solid tumors with a PIK3CA mutation. The study has two parts: first, finding the maximum tolerated dose (Part 1) and then expanding the trial to more patients at this dose (Part 2).

How Is the Trial Designed?

Group I: RLY-5836 Single Agent Arm Experimental Treatment 1 Intervention

RLY-5836 single agent arm for participants with unresectable or metastatic solid tumors

Group II: RLY-5836 + Ribociclib + Fulvestrant Arm Experimental Treatment 3 Interventions

RLY-5836 + ribociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group III: RLY-5836 + Palbociclib + Fulvestrant Arm Experimental Treatment 3 Interventions

RLY-5836 + palbociclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group IV: RLY-5836 + Fulvestrant Arm Experimental Treatment 2 Interventions

RLY-5836 + fulvestrant combination arm for participants with HR+, HER2- locally advanced or metastatic breast cancer

Group V: RLY-5836 + Abemaciclib + Fulvestrant Arm Experimental Treatment 3 Interventions

RLY-5836 + abemaciclib + fulvestrant triple combination arm for participants with HR+, HER2- locally advanced or metastatic 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/PMC11936477/

Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After ... Abemaciclib + fulvestrant significantly improved PFS after disease progression on previous CDK4/6i + ET in patients with HR+, HER2– ABC, offering an additional ...

2. onclive.com onclive.com/view/abemaciclib-fulvestrant-improves-pfs-across-hr-her2-advanced-breast-cancer-subgroups

Abemaciclib/Fulvestrant Improves PFS Across HR+/HER2 Abemaciclib plus fulvestrant improved PFS across subgroups in hormone receptor-positive, HER2-negative advanced breast cancer post-CDK4/6 ...

3. cancertherapyadvisor.com cancertherapyadvisor.com/news/clinical-trial-abemaciclib-plus-fulvestrant-in-hr-her2-advanced-breast-cancer/

Clinical Trial: Abemaciclib Plus Fulvestrant in HR+, HER2 Researchers are conducting a phase 3 trial to the effect of adding abemaciclib to fulvestrant in patients with advanced HR+, HER2- breast ...

4. withpower.com withpower.com/trial/phase-1-breast-neoplasms-2-2023-2d076

RLY-5836 for Advanced Breast Cancer · Info for Participants While there is no direct data on RLY-5836, similar treatments like fulvestrant have shown effectiveness in advanced breast cancer, especially after other ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12275406/

Abemaciclib in combination with endocrine therapy for the ... Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer. Curr Med Res Opin. 2021 ...

6. careacross.com careacross.com/clinical-trials/trial/NCT05759949

First-in-Human Study of RLY-5836 in Advanced Breast ... Description: Ribociclib 600 mg once daily is taken orally in combination with RLY-5836 and fulvestrant for 28-day cycles that include 21 days of treatment ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39249111/

Efficacy and Safety of Abemaciclib in Combination With ... This study comprehensively assesses the efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2- advanced or ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT213571

metastatic breast cancer administered abemaciclib plus ... Background: Abemaciclib is a selective inhibitor of CDK4 & 6 approved to treat HR+, HER2- metastatic breast cancer (MBC) patients (pts) as monotherapy and ...

9. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14526-w

Abemaciclib in combination with endocrine therapy for the ... Abemaciclib in combination with endocrine therapy for the treatment of HR-positive/HER2-negative locally advanced/metastatic breast cancer in ...