OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer (OPERA-01)

• ClinicalTrials.gov Identifier: NCT06016738
• Recruitment Status: Recruiting
• First Posted: August 30, 2023
• Last Update Posted: April 30, 2024
• Sponsor: Olema Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Olema Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: August 17, 2023
• First Posted Date: August 30, 2023
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: November 16, 2023
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2024)

• Dose-Selection Part: Incidence of adverse events [ Time Frame: From Date of Randomization up to 16 weeks ]
  To evaluate the number of participants with adverse events
• Dose-Selection Part: Incidence of dose reduction [ Time Frame: From Date of Randomization up to 16 weeks ]
  To evaluate the number of participants reducing the dose of palazestrant
• Dose-Selection Part: Incidence of drug discontinuation [ Time Frame: From Date of Randomization up to 16 weeks ]
  To evaluate the number of participants discontinuing palazestrant
• Trial: Progression-Free Survival (PFS) [ Time Frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years) ]
  To compare PFS, based on a Blinded Independent Review Committee (BIRC) assessment, between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1-mutation detected and ESR1-mutation not detected participants.

Original Primary Outcome Measures (submitted: August 29, 2023)

Progression-Free Survival (PFS) [ Time Frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years) ]

To compare PFS, based on a Blinded Independent Review Committee (BIRC) assessment, between arms of OP-1250 and standard of care treatment. This will be assessed separately in populations of ESR1 mutation detected and ESR1 mutation not detected participants.

Current Secondary Outcome Measures (submitted: February 8, 2024)

Trial: Overall Survival (OS) [ Time Frame: From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years) ]

To compare OS between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1 mutation detected and ESR1 mutation not detected participants.

Original Secondary Outcome Measures (submitted: August 29, 2023)

Overall Survival (OS) [ Time Frame: From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years) ]

To compare OS between arms of OP-1250 and standard of care treatment. This will be assessed separately in populations of ESR1 mutation detected and ESR1 mutation not detected participants.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer
• Official Title: A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)
• Brief Summary: This phase 3 clinical trial compares the safety and efficacy of palazestrant (OP-1250) to the standard-of-care options of fulvestrant or an aromatase inhibitor in women and men with breast cancer whose disease has advanced on one endocrine therapy in combination with a CDK4/6 inhibitor.

Detailed Description

This is an international, multicenter, randomized, open-label, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the safety and efficacy of palazestrant (OP-1250) as a single agent to the standard of care endocrine therapy: either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane).

This trial is seeking adult participants with ER+, HER2- advanced or metastatic breast cancer whose disease has relapsed or progressed on 1 or 2 prior lines of standard-of-care endocrine therapy for metastatic breast cancer. Prior lines of therapy must include one line of endocrine therapy in combination with a CDK 4/6 inhibitor. In the dose-selection part of the trial, approximately 120 participants will be randomized to one of the two doses of palazestrant or to the standard-of-care endocrine therapy. Thereafter, approximately 390 participants will be randomized to palazestrant at the selected dose or to the standard-of-care endocrine therapy.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Advanced Breast Cancer
• Metastatic Breast Cancer
• ER Positive Breast Cancer
• HER2 Negative Breast Carcinoma

Intervention

• Drug: Palazestrant
  Participants will be treated with palazestrant once daily on a 4 week (28 day) cycle. Doses evaluated in the dose-selection part will be 120 mg once daily and 90 mg once daily.
  Other Name: OP-1250
• Drug: Fulvestrant
  Participants will be treated with fulvestrant on C1D1, C1D15, and then on Day 1 of every subsequent 4 week (28 day) cycle
• Drug: Anastrozole
  Participants will be treated with anastrozole once daily on a 4 week (28 day) cycle
• Drug: Letrozole
  Participants will be treated with letrozole once daily on a 4 week (28 day) cycle
• Drug: Exemestane
  Participants will be treated with exemestane once daily on a 4 week (28 day) cycle

Study Arms

• Experimental: Palazestrant (OP-1250)
  Participants will receive Palazestrant
  Intervention: Drug: Palazestrant
• Active Comparator: Standard of Care Endocrine Therapy
  Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)
  Interventions:

  • Drug: Fulvestrant
  • Drug: Anastrozole
  • Drug: Letrozole
  • Drug: Exemestane

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 29, 2023): 510
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2027
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key inclusion criteria:

• Adult female or male participants.
• ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy.
• Evaluable disease (measurable disease or bone-only disease).
• Previously received a CDK4/6 inhibitor in combination with an endocrine therapy in the advanced setting. One additional line of ET as a monotherapy is allowed. Duration of the most recent prior ET must be at least 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, hepatic, and renal functions.
• Female participants can be pre-, peri- or postmenopausal.
• Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist.

Key exclusion criteria:

• Symptomatic visceral disease, imminent organ failure, or any other reason that makes the participant ineligible for endocrine monotherapy.
• Previously received chemotherapy in the advanced/metastatic setting.
• Previously received treatment with elacestrant or an investigational estrogen receptor-directed therapy.
• History of allergic reactions to study treatment.
• Any contraindications to the selected standard-of-care endocrine therapy in the local prescribing information.
• Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.
• Clinically significant comorbidities such as significant cardiac or cerebrovascular disease, gastrointestinal disorders that could affect absorption of study treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Olema Pharmaceuticals, Inc.; 415-651-7206; OPERA-01@olema.com

• Listed Location Countries: Argentina, Australia, Belgium, Hong Kong, Korea, Republic of, Malaysia, Portugal, Taiwan, Thailand, United States

Administrative Information

• NCT Number: NCT06016738
• Other Study ID Numbers: OP-1250-301; OPERA-01 ( Other Identifier: Olema Pharmaceuticals, Inc. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Olema Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Olema Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director, MD; Olema Pharmaceuticals, Inc.

• PRS Account: Olema Pharmaceuticals, Inc.
• Verification Date: April 2024