OP-1250 for Advanced Breast Cancer

(OPERA-01 Trial)

Recruiting at 152 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: Chemotherapy, Elacestrant

Disqualifiers: Visceral disease, CNS metastases, Cardiac, 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: Unknown

Duration: Up to 4 years

510 Participants Needed

Trial Summary

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, it mentions that participants must have previously received a CDK4/6 inhibitor with endocrine therapy, so you might need to continue certain treatments. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug OP-1250 (Palazestrant) for advanced breast cancer?

Research shows that letrozole, a component of the treatment, is effective in treating advanced breast cancer, with studies indicating it is more effective than tamoxifen and anastrozole in certain cases. Letrozole has been shown to improve disease-free survival and has a higher overall response rate compared to anastrozole in advanced breast cancer. ^{1 2 3 4 5}

What safety data exists for OP-1250 and related treatments in humans?

Letrozole and anastrozole, which are similar to OP-1250, have been used safely in postmenopausal women with breast cancer. Common mild side effects include hot flashes, joint pain, nausea, fatigue, and headaches. ^{1 2 6 7 8}

What makes OP-1250 (Palazestrant) unique compared to other breast cancer drugs?

OP-1250 (Palazestrant) is unique because it is a new type of drug being tested for advanced breast cancer, potentially offering a different mechanism of action compared to existing aromatase inhibitors like anastrozole, exemestane, and letrozole, which are already used for hormone receptor-positive breast cancer. ^{2 6 8 9 10}

What is the purpose of this trial?

This trial is testing a new drug called palazestrant to see if it works better than current treatments for adults with advanced breast cancer that has not responded to previous therapies. The drug aims to stop cancer growth by blocking estrogen.

Research Team

Medical Director, MD

Principal Investigator

Olema Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for adults with ER+/HER2- advanced breast cancer that's progressed after endocrine therapy and a CDK4/6 inhibitor. Participants need to be in good physical condition (ECOG 0 or 1), have proper organ function, and if male or pre-menopausal female, agree to take hormone-blocking injections.

Inclusion Criteria

I am an adult.

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

I've been treated with a CDK4/6 inhibitor and hormone therapy for advanced cancer.

Exclusion Criteria

My cancer is causing symptoms or organ failure, making me ineligible for hormone therapy.

I need urgent treatment for cancer spread to my brain or spinal cord.

I have no major health issues that could affect my treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Selection

Participants are randomized to one of the two doses of palazestrant or to the standard-of-care endocrine therapy to evaluate adverse events, drug discontinuation, and dose reduction

16 weeks

Treatment

Participants receive either palazestrant or standard-of-care endocrine therapy to compare overall survival and progression-free survival

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Anastrozole
• Exemestane
• Fulvestrant
• Letrozole
• OP-1250 (Palazestrant)

Trial Overview The study compares OP-1250, a new treatment option, against standard treatments like fulvestrant or aromatase inhibitors (Anastrozole, Letrozole, Exemestane) in patients whose breast cancer has worsened despite previous therapies.

Participant Groups

Group I: Palazestrant (OP-1250) Experimental Treatment 1 Intervention

Participants will receive Palazestrant

Group II: Standard of Care Endocrine Therapy Active Control 4 Interventions

Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)

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

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Olema Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

970+

Findings from Research

Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.

In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. Simpson, D., Curran, MP., Perry, CM.[2018]

The FACE trial is a large-scale study involving 4000 postmenopausal women with hormone receptor-positive, node-positive breast cancer, comparing the efficacy and safety of letrozole and anastrozole over a treatment period of up to 5 years.

The primary goal of the trial is to assess disease-free survival (DFS), while secondary objectives include evaluating overall survival (OS) and the time to distant metastases, which will provide comprehensive insights into the effectiveness of both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? Jonat, W., Mundhenke, C.[2018]

In a study involving 713 postmenopausal women with advanced breast cancer, letrozole (2.5 mg/day) demonstrated a significantly higher overall response rate (19.1%) compared to anastrozole (1 mg/day) (12.3%), indicating that letrozole may be more effective as a second-line endocrine therapy.

Despite the improved response rate with letrozole, both treatments showed no difference in time to progression, overall survival, or safety profiles, suggesting that while letrozole is more effective in eliciting responses, both drugs are well tolerated and have similar safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole. Rose, C., Vtoraya, O., Pluzanska, A., et al.[2022]

Letrozole, at both 2.5 mg and 10 mg doses, was effective as a neoadjuvant therapy for locally advanced breast cancer, with significant reductions in tumor volume observed in all patients, allowing for breast-conserving surgery.

There were no significant differences in efficacy between the two doses, and both were well-tolerated with no recordable side effects, indicating a favorable safety profile for letrozole in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Dixon, JM., Love, CD., Bellamy, CO., et al.[2022]

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[2018]

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

In a study involving 3697 postmenopausal women with hormone receptor-positive early breast cancer, the upfront treatment with aromatase inhibitors for 5 years did not show superior disease-free survival compared to a switch strategy of 2 years of tamoxifen followed by 3 years of aromatase inhibitors, with 5-year disease-free survival rates of 89.8% and 88.5%, respectively.

No significant differences in efficacy were found among the three aromatase inhibitors (anastrozole, exemestane, and letrozole), suggesting that factors like patient preference and tolerability should guide treatment decisions rather than efficacy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. De Placido, S., Gallo, C., De Laurentiis, M., et al.[2019]

Aromatase inhibitors like anastrozole, letrozole, and exemestane are now the preferred hormonal treatments for estrogen-receptor-positive, postmenopausal metastatic breast cancer, replacing older therapies such as tamoxifen.

Recent studies have confirmed the effectiveness of these aromatase inhibitors in managing breast cancer, highlighting their critical role in targeting the hormonal pathways involved in the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. Hamilton, A., Volm, M.[2018]

References

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

Letrozole: a review of its use in postmenopausal women with breast cancer. [2018]

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

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? [2018]

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

Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on letrozole or anastrozole. A phase II trial conducted by the Hellenic Group of Oncology (HELGO). [2022]

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

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Letrozole as primary medical therapy for locally advanced and large operable breast cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. [2018]

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

New developments in the treatment of postmenopausal breast cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. [2019]

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

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. [2018]