OP-1250 for Breast Cancer

No longer recruiting at 23 trial locations

Overseen By There may be multiple sites in this clinical trial.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Olema Pharmaceuticals, Inc.

Must be taking: Endocrine therapy

Disqualifiers: Gastrointestinal, Renal, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 106

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called OP-1250 (also known as Palazestrant) for individuals with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The goal is to assess the safety and effectiveness of OP-1250, both alone and at various doses. Participants should have previously tried at least one hormonal treatment for their condition and should not have certain issues like heart problems or infections. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must not have taken oral endocrine therapy within 2 weeks before starting the trial. Also, you should not have had chemotherapy, antibody therapy, or investigational therapy within certain time frames before the first dose.

Is there any evidence suggesting that OP-1250 is likely to be safe for humans?

Research has shown that OP-1250, also known as palazestrant, generally has a manageable safety profile. In some studies, patients experienced side effects such as nausea and a decrease in white blood cells, but these were manageable. The treatment was well-tolerated, even by patients who had undergone many other treatments. Most importantly, OP-1250 demonstrated promising results in effectiveness and safety, even in patients with advanced cancer. While these findings are encouraging, OP-1250 continues to undergo testing to confirm its safety and effectiveness in larger groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which often include hormone therapies, chemotherapy, and targeted therapies like HER2 inhibitors, OP-1250 is unique because it acts as an oral selective estrogen receptor degrader (SERD). This new mechanism targets and degrades estrogen receptors, which are often involved in the growth of breast cancer cells. Researchers are particularly excited about OP-1250 because it has the potential to be more effective and less invasive than current therapies, especially for patients with specific types of breast cancer that are resistant to other treatments. Additionally, OP-1250 offers a more convenient oral administration route, which can improve patient quality of life compared to more invasive treatment options.

What evidence suggests that OP-1250 might be an effective treatment for breast cancer?

Research has shown that OP-1250, also known as palazestrant, holds promise for treating advanced breast cancer. In this trial, participants will receive OP-1250 during different study phases. Studies have indicated that a daily dose of 120 mg helped nearly half of the patients by either shrinking their tumors or keeping them stable. On average, patients lived 4.8 months longer without their cancer worsening. These results suggest that OP-1250 could be a good option for those with hormone receptor-positive, HER2-negative breast cancer. ^{4 5 6 7 8}

Who Is on the Research Team?

Mark Shilkrut, MD

Principal Investigator

Olema Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced HR-positive, HER2-negative breast cancer who've had at least one hormonal treatment and six months of continuous endocrine therapy. Participants need good liver and kidney function, haven't had certain therapies recently, are not pregnant or breastfeeding, willing to use contraception, have a stable ECOG status (0 or 1), and no significant heart disease or infections.

Inclusion Criteria

My liver is working well.

I haven't had chemotherapy, antibody, or investigational therapy recently.

My kidney function is normal.

Exclusion Criteria

I have a serious heart condition.

I am currently being treated for a serious infection.

You have significant irregularities in your heart's electrical activity as shown on an ECG.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Dose Escalation

Evaluate the safety and pharmacokinetics of a range of OP-1250 doses to identify the maximum tolerated dose and/or recommended Phase 2 dose

28 days

Every 28 days

Phase I Dose Expansion

Evaluate the safety and pharmacokinetics of OP-1250 to confirm the recommended Phase 2 dose

28 days

Every 28 days

Phase II Monotherapy

Further explore the clinical activity, safety, and pharmacokinetics of OP-1250 monotherapy at the recommended Phase 2 dose and estimate preliminary anti-tumor efficacy

8 weeks

Every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Up to 42 days after end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• OP-1250

Trial Overview The study is testing different doses of OP-1250 to find the safest and most effective level for treating hormone receptor-positive, HER2-negative advanced breast cancer. It's an open-label trial meaning everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: OP-1250 Phase II Experimental Treatment 1 Intervention

This portion of the study further explores the clinical activity, safety, and PK of OP-1250 monotherapy at the RP2D and will estimate preliminary anti-tumor efficacy in 3 cohorts. Cohort A will enroll subjects with measurable disease without evidence of CNS metastases; Cohort B will enroll subjects with non-measurable (evaluable) disease without evidence of CNS metastases; and Cohort C will enroll subjects with evaluable disease (measurable and non-measurable) with CNS metastases.

Group II: OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion) Experimental Treatment 1 Intervention

Phase I Part A will evaluate the safety and pharmacokinetics (PK)of a range of OP-1250 doses to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Phase I Part B will evaluate the safety and PK of OP-1250 to confirm the RP2D dose.

Who Is Running the Clinical Trial?

Olema Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

970+

Published Research Related to This Trial

Neoadjuvant endocrine therapy for breast cancer is gaining acceptance, but there is still uncertainty about the best endpoints to measure its effectiveness, as short-term responses have not been validated as reliable indicators of long-term outcomes.

The LET 024 trial data suggests that combining clinical and biomarker endpoints, such as using Ki67 analysis to assess 'cell cycle response', could provide a more effective way to evaluate treatment success in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials. Tao, Y., Klause, A., Vickers, A., et al.[2018]

Elacestrant is the first oral selective estrogen receptor degrader (SERD) approved by the FDA for treating ER/PR-positive, HER2-negative metastatic breast cancer with ESR1 mutations, showing improved median progression-free survival compared to standard endocrine therapy in the EMERALD trial.

The drug acts as a mixed ER agonist/antagonist and has specific metabolic considerations, being primarily processed by CYP3A4, which can lead to drug interactions; dose adjustments are recommended for patients with moderate hepatic dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and pharmacokinetics of elacestrant. Beumer, JH., Foldi, J.[2023]

Elacestrant, a selective estrogen receptor degrader, was found to be safe and well tolerated in a study involving 140 postmenopausal women, with doses up to 1000 mg daily not reaching the maximum tolerated dose.

The drug showed good oral bioavailability and a half-life of 27 to 47 hours, allowing for once-daily dosing, while effectively engaging estrogen receptors and demonstrating some ability to cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. Conlan, MG., de Vries, EFJ., Glaudemans, A., et al.[2021]

Elacestrant (RAD1901) effectively degrades estrogen receptors and inhibits the growth of estrogen receptor-positive (ER+) breast cancer cells in both laboratory and patient-derived models, showing significant antitumor activity.

The combination of elacestrant with other therapies like palbociclib or everolimus enhances its efficacy, suggesting it could be a valuable treatment option for patients with ER+ breast cancer, including those with resistant mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Bihani, T., Patel, HK., Arlt, H., et al.[2018]

Preoperative endocrine therapy for ER-positive breast cancer can achieve a response rate of nearly 70% within about 3 months, offering a less toxic alternative to neoadjuvant chemotherapy, which has no demonstrated survival benefit over adjuvant therapy.

Further randomized clinical trials are needed to establish the effectiveness of preoperative endocrine therapy compared to traditional adjuvant therapy, determine the optimal treatment duration, and identify additional predictive factors for patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative endocrine therapy for breast cancer. Cheung, KL., Howell, A., Robertson, JF.[2019]

Citations

1. ir.olema.com ir.olema.com/news-releases/news-release-details/olema-oncology-presents-updated-clinical-results-palazestrant

Release Details Palazestrant combined with ribociclib showed promising clinical activity including tumor responses, prolonged disease stabilization, and progression-free ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12210654/

advanced or metastatic breast cancer: phase 1/2 study results The RP2D of 120 mg/day palazestrant demonstrated evidence of antitumor activity, with a CBR of 45.7% and a median PFS of 4.8 months in the ...

3. 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/ ... “We are very pleased with these latest data showing compelling progression-free survival and favorable tolerability of palazestrant plus ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS1131

OPERA-01: A randomized, open-label, phase 3 study of ... As monotherapy, palazestrant showed a tolerable safety profile, favorable pharmacokinetics and encouraging antitumor efficacy in heavily- ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)01395-9/fulltext

382MO Updated results from the phase I/II study of OP ... By March 17, 2023, of 86 pts on OP-1250 (120 mg), 66% had ≥2 prior lines of ET, 30% prior chemotherapy, 67% prior fulvestrant, and 98% prior cyclin-dependent ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40598566/

Palazestrant, a novel oral Complete Estrogen Receptor ... At 120 mg/day, the median progression-free survival was 4.8 months (95% CI, 3.5-7.1) overall and 5.6 months (95% CI, 4.8-NE) among patients with ...

7. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-02049-y

Palazestrant, a novel oral Complete Estrogen Receptor ... Palazestrant demonstrated a manageable safety profile, with antitumor activity observed in patients with heavily pretreated cancers with wild- ...

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

212P A phase Ib/II study of palazestrant (OP-1250) in ... At time of the data cutoff, 26 pts (79%) were on treatment. The most common (≥25%) treatment-emergent adverse events (TEAEs) were nausea, neutropenia (G4: 2 pts ...