RLY-2608 + Fulvestrant for Breast Cancer

Recruiting at 38 trial locations

Overseen By Relay Therapeutics Inc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Relay Therapeutics, Inc.

Must be taking: GnRH agonist

Must not be taking: Antihyperglycemics, PI3K inhibitors

Disqualifiers: Diabetes, Cardiovascular disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

930 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RLY-2608, either alone or with other drugs like fulvestrant (also known as Faslodex, a hormone therapy), for individuals with certain types of breast cancer or other advanced solid tumors. Researchers aim to determine the safest dose and evaluate the treatment's effectiveness. Suitable candidates include those with hard-to-treat or advanced cancers that haven't responded to other treatments, particularly if they have a specific mutation called PIK3CA. As a Phase 1 trial, this research focuses on understanding the treatment's effects 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 Type 1 or Type 2 diabetes requiring medication, you may not be eligible. It's best to discuss your specific 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 was safe in earlier studies. Patients with certain types of breast cancer (those with PIK3CA mutations, hormone receptor-positive, and HER2-negative) experienced manageable side effects. This indicates that patients could tolerate the treatment without major issues. The combination also demonstrated promising results in combating the cancer, suggesting its effectiveness. Although some side effects were reported, they were not severe enough to outweigh the benefits observed in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HR+ HER2- locally advanced or metastatic breast cancer because they offer a novel approach compared to standard options like hormone therapies, chemotherapy, or CDK4/6 inhibitors. RLY-2608 is a new active ingredient that, when combined with fulvestrant, potentially enhances effectiveness against cancer cells. Additionally, the combinations with palbociclib, ribociclib, and PF-07220060 in varying doses aim to optimize treatment by targeting cancer cell growth more precisely. This tailored approach could lead to more effective and personalized treatment options for patients.

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

Research shows that combining RLY-2608 and fulvestrant holds promise for treating HR-positive, HER2-negative breast cancer with a PIK3CA mutation. Studies have demonstrated that this combination allows patients to live without their cancer worsening for an average of 9.2 months. In this trial, participants will receive RLY-2608 and fulvestrant, with some groups also receiving additional drugs like palbociclib or ribociclib, which enhance treatment effects. RLY-2608 targets a specific change in the PI3Kα protein, which often promotes cancer growth. Fulvestrant has already proven successful in treating advanced breast cancer. Together, these treatments offer a focused approach to combating this type of cancer. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or breast cancer that can't be removed by surgery, have worsened despite standard treatments, or who cannot tolerate such treatments. Participants must have a specific gene mutation (PIK3CA), be in good physical condition (ECOG 0-1), and not have certain health issues like uncontrolled diabetes or heart disease.

Inclusion Criteria

I stopped a PI3Kα inhibitor treatment due to side effects, not because my disease got worse.

I can provide a sample of my tumor or am willing to have a biopsy for testing.

I have breast cancer that cannot be surgically removed or cured, and it is hormone receptor positive and HER2 negative.

Exclusion Criteria

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

My family has a history of prolonged QT syndrome.

I have a history of abnormal heart rhythms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of RLY-2608, alone or in combination with fulvestrant and other inhibitors, to determine the maximum tolerated dose

8-12 weeks

Dose Expansion

Participants receive the recommended Phase 2 dose of RLY-2608, alone or in combination, to further evaluate safety and preliminary antineoplastic 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

• Fulvestrant
• RLY-2608

Trial Overview

The study tests RLY-2608 alone and combined with fulvestrant, plus CDK4/6 inhibitors palbociclib or ribociclib in patients with hormone receptor-positive, HER2-negative advanced breast cancer. It aims to find the safest dose that works best (dose escalation) and then see how well it works at this dose (dose expansion).

How Is the Trial Designed?

Group I: RLY-2608+fulvestrant+ribo600mg for HR+HER2- locally advanced metastatic breast cancer Experimental Treatment 3 Interventions

Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation.

Group II: RLY-2608+fulvestrant+ribo400mg for HR+HER2- locally advanced metastatic breast cancer Experimental Treatment 3 Interventions

Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation.

Group III: RLY-2608+fulvestrant+palbo125mg for HR+HER2- locally advanced metastatic breast cancer Experimental Treatment 3 Interventions

Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation.

Group IV: RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancer Experimental Treatment 3 Interventions

Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation

Group V: RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancer Experimental Treatment 3 Interventions

Oral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation

Group VI: RLY-2608 for patients with unresectable or metastatic solid tumors Experimental Treatment 2 Interventions

Multiple doses of RLY-2608 for oral administration.

Group VII: RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancer Experimental Treatment 2 Interventions

Oral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation.

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Relay Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

1,900+

Published Research Related to This Trial

Fulvestrant is an effective estrogen receptor antagonist for postmenopausal women with advanced breast cancer who have progressed after previous endocrine therapies, as demonstrated in a Compassionate Use Programme with diverse patient cases.

Clinical experience from the Compassionate Use Programme aligns with clinical trial data, indicating that fulvestrant is a valuable treatment option even for patients with challenging disease characteristics, such as visceral metastases and HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case studies of fulvestrant ("Faslodex") in postmenopausal women with advanced breast cancer. Abram, P., Maass, N., Rea, D., et al.[2018]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

A study involving 134 patients with metastatic estrogen receptor-positive breast cancer identified a novel gene signature that can predict response to fulvestrant treatment, highlighting potential new therapeutic targets.

Increased expression of the gene TFAP2C was linked to a decreased response to fulvestrant, suggesting it could serve as a predictive biomarker for treatment outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor-Positive Breast Cancer. Jeselsohn, R., Barry, WT., Migliaccio, I., et al.[2018]

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06982521

NCT06982521 | Phase 3 Study of RLY-2608 + Fulvestrant ...

This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + fulvestrant to capivasertib + ...

2.

curetoday.com

curetoday.com/view/understanding-the-side-effects-of-rly-2608-in-hr-her2-breast-cancer

Understanding the Side Effects of RLY-2608 in HR+, HER2

Dr. Sarah Sammons discusses side effects associated with RLY-2608, and how it effects patients with HR-positive, HER2-negative advanced breast ...

3.

onclive.com

onclive.com/view/rly-2608-plus-fulvestrant-demonstrates-efficacy-in-pik3ca-mutated-hr-her2-advanced-breast-cancer

RLY-2608 Plus Fulvestrant Demonstrates Efficacy in ...

Sarah Sammons, MD, discusses data from the phase 1 ReDiscover trial of RLY-2608 plus fulvestrant in HR-positive, HER2-negative breast cancer.

4.

onclive.com

onclive.com/view/rly-2608-fulvestrant-yields-early-clinical-activity-in-pi3k--mutated-hr-her2-breast-cancerolid-tumors

RLY-2608/Fulvestrant Yields Early Clinical Activity in PI3Kα ...

RLY-2608 plus fulvestrant achieved a median PFS of 9.2 months in PI3Kα-mutated, HR-positive, HER2-negative metastatic breast cancer patients.

5.

ir.relaytx.com

ir.relaytx.com/news-releases/news-release-details/relay-therapeutics-announces-updated-data-rly-2608-fulvestrant

Relay Therapeutics Announces Updated Data for RLY ...

They show a median progression free survival (PFS) of 11.0 months in second line (2L) patients with PI3Kα-mutated, HR+, HER2- locally advanced ...