OP-1250 for Breast Cancer

Recruiting at 22 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

153 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called OP-1250 in adults with a specific type of advanced breast cancer. The drug aims to block certain receptors on cancer cells to stop them from growing. The study will determine the best dose and check for any side effects.

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.

What data supports the effectiveness of the drug OP-1250 for breast cancer?

Research shows that endocrine therapy, which includes drugs that block estrogen, can be effective in treating hormone receptor-positive breast cancer. Studies have found that such treatments can shrink tumors and make them operable, with a response rate of up to 70% in some cases. ^{1 2 3 4 5}

What makes the drug OP-1250 (Palazestrant) unique for breast cancer treatment?

OP-1250, also known as Palazestrant, is a novel oral selective estrogen receptor degrader (SERD) that targets and degrades estrogen receptors in breast cancer cells, which is different from traditional endocrine therapies that only block these receptors. This drug is particularly beneficial for patients with ESR1 mutations, which are often resistant to standard endocrine therapies. ^{6 7 8 9 10}

Research Team

Mark Shilkrut, MD

Principal Investigator

Olema Pharmaceuticals, Inc.

Gurpreet Mathauda-Sahota, PharmD

Principal Investigator

Olema Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evidence-based neoadjuvant endocrine therapy for breast cancer. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in high-risk HR+ /HER2- early breast cancer patients treated with endocrine therapy with or without palbociclib within the randomized PENELOPEB study. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

[CURRENT PERSPECTIVE ON SYSTEMIC THERAPY FOR BREAST CANCER]. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Preoperative endocrine therapy for breast cancer. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating Elacestrant in the Management of ER-Positive, HER2-Negative Advanced Breast Cancer: Evidence to Date. [2023]

7. United States 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. [2018]

8. Greece pubmed.ncbi.nlm.nih.gov

Modulation of receptor levels in canine breast tumors by administration of tamoxifen and etretinate either alone or in combination. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Pharmacology and pharmacokinetics of elacestrant. [2023]

10. France pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. [2021]