Palazestrant + Ribociclib for Breast Cancer

(OPERA-02 Trial)

Not yet recruiting at 9 trial locations

Overseen By Olema Pharmaceuticals, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Olema Pharmaceuticals, Inc.

Must be taking: GnRH agonist

Must not be taking: Fulvestrant, Elacestrant

Disqualifiers: CNS metastases, Allergic reactions, 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: 28

Duration: Up to 3.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of a new drug combination for treating advanced breast cancer. It compares palazestrant (a potential new drug) and ribociclib with the current treatment option of letrozole and ribociclib. The researchers seek to determine if the new combination is more effective for individuals who have not yet received any treatment for their advanced breast cancer. Suitable participants have advanced breast cancer that cannot be cured with surgery and have not yet undergone any systemic anti-cancer treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received any prior systemic anti-cancer treatment for advanced breast cancer to participate.

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

Research has shown that the combination of palazestrant and ribociclib is generally well-tolerated. In studies with 72 patients, this treatment did not reveal any new safety concerns. Most participants managed the treatment well, experiencing no unexpected side effects. This suggests that the treatment is considered safe based on current information.

While palazestrant remains under study, ribociclib is already approved for treating breast cancer, providing some confidence in the combination's safety due to ribociclib's well-understood safety profile. However, ongoing trials are essential to ensure the treatment's safety for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about palazestrant for breast cancer because it offers a fresh approach to treatment with its novel mechanism of action. Unlike standard therapies like letrozole, which target estrogen receptors directly, palazestrant acts as a selective estrogen receptor degrader (SERD). This means it not only blocks the receptor but also helps break it down, potentially leading to more effective inhibition of cancer cell growth. Additionally, combining palazestrant with ribociclib, a CDK4/6 inhibitor, could enhance its effectiveness by further disrupting cancer cell division, offering hope for improved outcomes compared to existing treatments.

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

Studies have shown that combining palazestrant and ribociclib holds promise for treating advanced breast cancer. In earlier research, patients taking this combination experienced an average of 15.5 months before their cancer worsened. This indicates that the treatment helped prevent cancer progression for over a year, on average. Additionally, the clinical benefit rate (CBR), which measures how many people saw their cancer stop growing or shrink, ranged from 79% to 85%. In this trial, participants will receive either palazestrant with ribociclib and a letrozole-matching placebo or letrozole with ribociclib and a palazestrant-matching placebo. These findings suggest that palazestrant with ribociclib could effectively manage breast cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

Olema Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with ER+/HER2- advanced breast cancer that can't be cured by surgery or radiation. They should have measurable disease, good blood, liver, and kidney function. Women of any menopausal status and men willing to use hormone therapy can join. It's not for those who've had prior systemic anti-cancer treatments.

Inclusion Criteria

My breast cancer is ER positive, HER2 negative, advanced, and cannot be cured with surgery or radiation.

My cancer can be measured or is only in my bones.

I am an adult.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either palazestrant with ribociclib or letrozole with ribociclib

Up to 3.5 years

Every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 42 days after end of treatment

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Palazestrant
• Ribociclib

Trial Overview The study compares palazestrant plus ribociclib against letrozole plus ribociclib in treating advanced breast cancer without previous systemic treatment. It's a phase 3 trial, which means it's testing the effectiveness and safety of this combination on a larger group of people.

How Is the Trial Designed?

Group I: Palazestrant Experimental Treatment 3 Interventions

Participants will receive palazestrant, ribociclib and letrozole-matching placebo

Group II: Letrozole Active Control 3 Interventions

Participants will receive letrozole, ribociclib and palazestrant-matching placebo

Who Is Running the Clinical Trial?

Olema Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

970+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. ir.olema.com ir.olema.com/news-releases/news-release-details/olema-oncology-announces-new-data-phase-1b2-trial-palazestrant

Olema Oncology Announces New Data from the Phase 1b/ ... Palazestrant in combination with ribociclib demonstrated encouraging activity across all dose cohorts and subgroups; Median PFS was 15.5 ...

2. cancernetwork.com cancernetwork.com/view/palazestrant-combo-shows-preliminary-activity-in-er-her2-breast-cancer

Palazestrant Combo Shows Preliminary Activity in ER+/HER2 Among those who received palazestrant at 120 mg, the median progression-free survival (PFS) was 15.5 months (95% CI, 9.0-not evaluable [NE]) for ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P2-09-16/752462/Abstract-P2-09-16-A-Phase-1b-2-study-of

A Phase 1b/2 study of palazestrant (OP-1250) in combination ... Clinical benefit rates (CBR) were 79% among all CBR-eligible pts (n=29) and 78% among the CBR-eligible patients with prior CDK4/6i treatment (n= ...

4. targetedonc.com targetedonc.com/view/palazestrant-with-ribociclib-shows-promising-early-results-in-er-her2--mbc

Palazestrant With Ribociclib Shows Promising Early ... The combination led to a clinical benefit rate (CBR) of 85% across all patients who were eligible (11/13), 83% in patients with ESR1-mutated ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07085767

Study Details | NCT07085767 | Palazestrant in ... The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: ...

6. esmoopen.com esmoopen.com/article/S2059-7029(24)01002-0/fulltext

212P A phase Ib/II study of palazestrant (OP-1250) in ... Conclusions. Palazestrant plus ribociclib was well tolerated and enrollment is ongoing. No new safety signals were identified. Antitumor activity and clinical ...