A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer

• ClinicalTrials.gov Identifier: NCT04505826
• Recruitment Status: Active, not recruiting
• First Posted: August 10, 2020
• Last Update Posted: August 22, 2023
• Sponsor: Olema Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Olema Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: July 21, 2020
• First Posted Date: August 10, 2020
• Last Update Posted Date: August 22, 2023
• Actual Study Start Date: August 13, 2020
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2023)

• Dose Limiting Toxicities (DLT) [ Time Frame: The first 28 days of treatment ]
  To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of OP-1250, the incidence of DLTs will be assessed.
• Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250 [ Time Frame: Up to 42 days after end of treatment ]
  Characterize the incidence, nature and severity of TEAEs and SAEs of OP-1250 according to NCI-CTCAE version 5.0
• Pharmacokinetics of OP-1250 [ Time Frame: Every 28 days ]
  Plasma concentrations of OP-1250 will be assessed at predefined intervals
• Anti-tumor activity of OP-1250 [ Time Frame: Every 8 weeks ]
  Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines

Original Primary Outcome Measures (submitted: August 6, 2020)

Determine MTD and/or RP2D of OP-1250 when used as a single agent [ Time Frame: Up to one year ]

Number of patients with DLT as defined in the protocol

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

Descriptive Information

• Brief Title: A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer
• Official Title: A Phase I Dose Escalation and Dose Expansion and Phase II Monotherapy Open-label, First-in-Human, Multicenter Study of OP-1250 in Adult Subjects With Advanced and/or Metastatic Hormone Receptor (HR)-Positive, HER2-negative Breast Cancer
• Brief Summary: This clinical trial is a Phase I dose escalation and dose expansion and Phase II monotherapy open-label, first-in-human, multicenter study of OP-1250 in adult subjects with advanced and/or metastatic hormone receptor (HR)-positive, her2-negative breast cancer.
• Detailed Description: This is a Phase I dose escalation and dose expansion and Phase II monotherapy open--label, first--in--human study to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D), to characterize the safety and pharmacokinetic (PK) profile, and to estimate the preliminary anti-tumor activity of OP-1250 as a single agent in adult subjects with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic or locally advanced breast cancer. This study comprises 2 Phases: Phase I (Part A [Dose Escalation] and Part B [Dose Expansion]) and Phase II. Additionally, all subjects (Phase I and Phase II) will be eligible to participate in 1 of 2 sub-studies. Patients must have received at least 1 prior hormonal regimen and at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic disease. Patients will be evaluated for treatment emergent adverse events (AEs) during study participation, and toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hormone Receptor Positive Breast Carcinoma
• HER2-negative Breast Cancer

Intervention

Drug: OP-1250

Complete Estrogen Receptor ANtagonist (CERAN)

Study Arms

• Experimental: OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion)
  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.
  Intervention: Drug: OP-1250
• Experimental: OP-1250 Phase II

  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.

  Intervention: Drug: OP-1250

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 20, 2023): 153
• Original Estimated Enrollment (submitted: August 6, 2020): 94
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Must have received at least 1 prior hormonal regimen and at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic disease
• Must not have received prior oral endocrine therapy < 2 weeks prior to first dose
• Must not have received prior, chemotherapy in 2 weeks or within 5 half-lives whichever is earlier, antibody therapy within 4 weeks or investigational therapy within 4 weeks or 5 half-lives whichever is earlier, prior to the first dose
• Adequate hepatic function
• Adequate renal function
• Normal coagulation panel
• Willingness to use effective contraception

Exclusion Criteria:

• Gastrointestinal disease
• Significant renal disease
• Significant cardiovascular disease
• Significant ECG abnormalities
• Ongoing systemic bacterial, fungal, or viral infection (requiring antimicrobial therapy)
• Pregnancy or breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT04505826
• Other Study ID Numbers: OP-1250-001
• Has Data Monitoring Committee: No

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: Mark Shilkrut, MD; Olema Pharmaceuticals, Inc.
• Study Director: Gurpreet Mathauda-Sahota, PharmD; Olema Pharmaceuticals, Inc.

• PRS Account: Olema Pharmaceuticals, Inc.
• Verification Date: August 2023