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Phase 1b Combo w/ Ribociclib and Alpelisib

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ClinicalTrials.gov Identifier: NCT05508906
Recruitment Status : Recruiting
First Posted : August 19, 2022
Last Update Posted : January 11, 2024
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Olema Pharmaceuticals, Inc.

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Advanced Breast Cancer HR-positive Breast Cancer HER2-negative Breast Cancer Drug: OP-1250 Drug: Ribociclib Drug: Alpelisib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Treatment Group 1: OP-1250 in combination with ribociclib (n= 60)

Treatment Group 2: OP-1250 in combination with alpelisib (n= 30)

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 31, 2022
Estimated Primary Completion Date : August 31, 2024
Estimated Study Completion Date : August 31, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Ribociclib

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 Name: 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 Name: PIQRAY




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) [ Time Frame: The first 28 days of treatment ]
    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.

  2. 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) [ Time Frame: Up to 35 days after end of treatment ]
    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.

  3. Pharmacokinetics (PK) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) [ Time Frame: Every 28 days ]
    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.


Secondary Outcome Measures :
  1. Preliminarily assess the anti-tumor activity of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) [ Time Frame: Up to 1 year ]
    Tumor response will be evaluated in patients with measurable or evaluable disease using RECISTv1.1 guidelines.

  2. Evaluate clinical benefit rate (CBR) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) [ Time Frame: Up to 1 year ]
    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.

  3. Evaluate duration of response (DOR) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) [ Time Frame: Up to 1 year ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05508906


Contacts
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Contact: There may be multiple sites in this clinical trial OP-1250-003 Study 415 651 7206 clinical@olema.com

Locations
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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Research Coordinator         
United States, California
University of California San Francisco Health Recruiting
San Francisco, California, United States, 94158
Contact: Research Coordinator         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Research Coordinator         
United States, Florida
Advent Health Hematology and Oncology Recruiting
Orlando, Florida, United States, 32804
Contact: Research Coordinator         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Research Coordinator         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Research Coordinator         
United States, Michigan
Henry Ford Health Recruiting
Detroit, Michigan, United States, 48126
Contact: Research Coordinator         
United States, Minnesota
Regents of the University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Research Coordinator         
United States, Missouri
Washington University, School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Research Coordinator         
United States, New York
Ichan School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Research Coordinator         
United States, North Carolina
Atrium Health Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Research Coordinator         
United States, Tennessee
Henry-Joyce Cancer Clinic, The Vanderbilt Clinic Recruiting
Nashville, Tennessee, United States, 37232
Contact: Research Coordinator         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Research Coordinator         
United States, Washington
Northwest Medical Specialties Recruiting
Tacoma, Washington, United States, 98405
Contact: Research Coordinator         
Australia, Western Australia
Breast Cancer Research Center- Western Australia Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Research Coordinator         
Australia
Macquarie Health Recruiting
New South Wales, Australia, 2109
Contact: Research Coordinator         
Sponsors and Collaborators
Olema Pharmaceuticals, Inc.
Novartis
Investigators
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Study Director: Mark Shilkrut, M.D. Olema Pharmaceuticals, Inc.
Study Director: Eric Park, M.D. Olema Pharmaceuticals, Inc.
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Responsible Party: Olema Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05508906    
Other Study ID Numbers: OP-1250-003
First Posted: August 19, 2022    Key Record Dates
Last Update Posted: January 11, 2024
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases