Phase 1b Combo w/ Ribociclib and Alpelisib

A Phase 1b Open-Label Multicenter Study of OP-1250 in Combination With the CDK4/6 Inhibitor Ribociclib or With the PI3K Inhibitor Alpelisib in Adult Subjects With Advanced and/or Metastatic HR Positive, HER2 Negative Breast Cancer

This is a Phase 1b open-label, 2-part study in 2 treatment groups. The 2 treatment groups are as follows:

Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).

Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation).

Study Overview

• Status: Recruiting
• Conditions: Advanced Breast Cancer; Metastatic Breast Cancer; HR-positive Breast Cancer; HER2-negative Breast Cancer
• Intervention / Treatment: Drug: OP-1250; Drug: Ribociclib; Drug: Alpelisib

Detailed Description

Part 1 (Dose Escalation): This part will evaluate the safety and pharmacokinetics (PK) of a range of doses of OP-1250 administered orally (PO) every day (QD) to subjects in combination with either 600 mg of ribociclib administered PO QD (Treatment Group 1) or with 300 mg of alpelisib administered PO QD (Treatment Group 2) to determine the recommended phase 2 dose (RP2D). The dose escalation phase will evaluate 3 to 6 subjects per cohort who are sequentially enrolled and monitored for DLTs during the first cycle of study treatment. Each cohort will be reviewed for safety, PK, and dose-limiting toxicity DLTs. The DLT observation may be extended to 2 cycles.

Part 2 (Dose Expansion): This part of the study will further evaluate the safety and PK of OP-1250 at the RP2D in combination with either ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) and provide an exploratory estimate of anti-tumor activity of the combinations.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial OP-1250-003 Study; Phone Number: 415 651 7206; Email: clinical@olema.com

Study Locations

• Australia
  • New South Wales, Australia, 2109
    • Recruiting
    • Macquarie Health
    • Contact: Research Coordinator
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Breast Cancer Research Center- Western Australia
      • Contact: Research Coordinator
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
      • Contact: Research Coordinator
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco Health
      • Contact: Research Coordinator
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
      • Contact: Research Coordinator
  • Florida
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Advent Health Hematology and Oncology
      • Contact: Research Coordinator
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Research Coordinator
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Research Coordinator
  • Michigan
    • Detroit, Michigan, United States, 48126
      • Recruiting
      • Henry Ford Health
      • Contact: Research Coordinator
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Regents of the University of Minnesota
      • Contact: Research Coordinator
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University, School of Medicine
      • Contact: Research Coordinator
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Ichan School of Medicine at Mount Sinai
      • Contact: Research Coordinator
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Atrium Health Levine Cancer Institute
      • Contact: Research Coordinator
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Henry-Joyce Cancer Clinic, The Vanderbilt Clinic
      • Contact: Research Coordinator
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Research Coordinator
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Northwest Medical Specialties
      • Contact: Research Coordinator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female or male aged >18 years.
• Willing and able to participate and comply with all study requirements
• Histologically- or cytologically-confirmed advanced or MBC
• HR+/HER2- disease, as determined in the most recently obtained archival tumor tissue sample from a metastatic site, using locally accepted criteria by the local pathology report
• Evaluable disease (measurable and non-measurable): Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).-Subject must have received at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic breast cancer
• Life expectancy ≥6 months, as judged by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Has received no more than 1 prior hormonal regimen (Treatment Group 1). Has received no more than 2 prior hormonal regimens (Treatment Group 2) for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed.
• Has received no more than 1 prior chemotherapy (which includes antibody drug conjugates) for locally advanced or metastatic breast cancer.

Exclusion Criteria:

• Prior or concurrent malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
• History of cerebral vascular disease within 6 months prior to the first administration of study drug dose
• History of a pulmonary embolism, or deep venous thrombosis within the last 6 months, or subject has an increased risk of thrombosis as determined by the investigator
• History of pneumonitis or interstitial lung disease
• Leptomeningeal disease or spinal cord compression
• Medical history or ongoing gastrointestinal disorders that could affect absorption of oral therapeutics
• Known human immunodeficiency virus infection
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (eg, hepatitis B or hepatitis C virus), current alcohol abuse, or cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OP-1250 with Ribociclib; Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).	Drug: OP-1250; OP-1250 is a small molecule and a CERAN being developed for the treatment of patients with advanced or metastatic HR+ and HER2- breast cancer.; Drug: Ribociclib; All subjects in Treatment Group 1 will receive OP-1250 in combination with ribociclib.; Other Names: KISQALI
Experimental: OP-1250 with Alpelisib; Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation)	Drug: OP-1250; OP-1250 is a small molecule and a CERAN being developed for the treatment of patients with advanced or metastatic HR+ and HER2- breast cancer.; Drug: Alpelisib; All subjects in Treatment Group 2 will receive OP-1250 in combination with alpelisib.; Other Names: PIQRAY

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs)	To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2), the incidence of DLTs will be assessed in the Dose Escalation part (Part 1) of the study.	The first 28 days of treatment
Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)	Characterize the incidence, nature and severity of TEAEs and SAEs of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) according to NCI-CTCAE version 5.0.	Up to 35 days after end of treatment
Pharmacokinetics (PK) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)	To assess the PK of OP-1250 in combination with ribociclib or alpelisib, plasma levels of OP-1250 (and potential metabolites) and ribociclib (Treatment Group 1) and plasma levels of OP-1250 (and potential metabolites) and alpelisib (Treatment Group 2) will be assessed at predefined intervals.	Every 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminarily assess the anti-tumor activity of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)	Tumor response will be evaluated in patients with measurable or evaluable disease using RECISTv1.1 guidelines.	Up to 1 year
Evaluate clinical benefit rate (CBR) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)	CBR will be assessed as proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) with duration of at least 24 weeks.	Up to 1 year
Evaluate duration of response (DOR) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)	DOR will be calculated as the number of days from the start date of PR or CR (whichever response is achieved first) to the first date that progressive disease is documented.	Up to 1 year

Collaborators and Investigators

• Sponsor: Olema Pharmaceuticals, Inc.
• Collaborators: Novartis
• Investigators: Study Director: Mark Shilkrut, M.D., Olema Pharmaceuticals, Inc.; Study Director: Eric Park, M.D., Olema Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: OP-1250-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No