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Phase 1b Combo w/ Ribociclib and Alpelisib

Primary Purpose

Metastatic Breast Cancer, Advanced Breast Cancer, HR-positive Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
OP-1250
Ribociclib
Alpelisib
Sponsored by
Olema Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 2 prior hormonal regimens for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed.
  • Has received no more than 1 prior chemotherapy 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

Sites / Locations

  • Banner MD Anderson Cancer CenterRecruiting
  • University of California San Francisco HealthRecruiting
  • University of Colorado Cancer CenterRecruiting
  • Advent Health Hematology and OncologyRecruiting
  • University of IowaRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • Henry Ford HealthRecruiting
  • Regents of the University of MinnesotaRecruiting
  • Washington University, School of MedicineRecruiting
  • Ichan School of Medicine at Mount SinaiRecruiting
  • Atrium Health Levine Cancer InstituteRecruiting
  • Henry-Joyce Cancer Clinic, The Vanderbilt ClinicRecruiting
  • MD Anderson Cancer CenterRecruiting
  • Northwest Medical SpecialtiesRecruiting
  • Breast Cancer Research Center- Western AustraliaRecruiting
  • Macquarie HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

OP-1250 with Ribociclib

OP-1250 with Alpelisib

Arm Description

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)

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
August 16, 2022
Last Updated
September 25, 2023
Sponsor
Olema Pharmaceuticals, Inc.
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT05508906
Brief Title
Phase 1b Combo w/ Ribociclib and Alpelisib
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2022 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Olema Pharmaceuticals, Inc.
Collaborators
Novartis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Advanced Breast Cancer, HR-positive Breast Cancer, HER2-negative Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Treatment Group 1: OP-1250 in combination with ribociclib Treatment Group 2: OP-1250 in combination with alpelisib
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
OP-1250 with Ribociclib
Arm Type
Experimental
Arm Description
Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).
Arm Title
OP-1250 with Alpelisib
Arm Type
Experimental
Arm Description
Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation)
Intervention Type
Drug
Intervention Name(s)
OP-1250
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Other Intervention Name(s)
KISQALI
Intervention Description
All subjects in Treatment Group 1 will receive OP-1250 in combination with ribociclib.
Intervention Type
Drug
Intervention Name(s)
Alpelisib
Other Intervention Name(s)
PIQRAY
Intervention Description
All subjects in Treatment Group 2 will receive OP-1250 in combination with alpelisib.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (DLTs)
Description
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.
Time Frame
The first 28 days of treatment
Title
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)
Description
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.
Time Frame
Up to 35 days after end of treatment
Title
Pharmacokinetics (PK) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)
Description
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.
Time Frame
Every 28 days
Secondary Outcome Measure Information:
Title
Preliminarily assess the anti-tumor activity of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)
Description
Tumor response will be evaluated in patients with measurable or evaluable disease using RECISTv1.1 guidelines.
Time Frame
Up to 1 year
Title
Evaluate clinical benefit rate (CBR) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)
Description
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.
Time Frame
Up to 1 year
Title
Evaluate duration of response (DOR) of OP-1250 when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2)
Description
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.
Time Frame
Up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 2 prior hormonal regimens for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed. Has received no more than 1 prior chemotherapy 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
There may be multiple sites in this clinical trial OP-1250-003 Study
Phone
415 651 7206
Email
clinical@olema.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Shilkrut, MD
Organizational Affiliation
Olema Pharmaceuticals, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Gurpreet Mathauda-Sahota, PharmD
Organizational Affiliation
Olema Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
University of California San Francisco Health
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Advent Health Hematology and Oncology
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Henry Ford Health
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48126
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Regents of the University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Washington University, School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Ichan School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Atrium Health Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Henry-Joyce Cancer Clinic, The Vanderbilt Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Northwest Medical Specialties
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Breast Cancer Research Center- Western Australia
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator
Facility Name
Macquarie Health
City
New South Wales
ZIP/Postal Code
2109
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Coordinator

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Phase 1b Combo w/ Ribociclib and Alpelisib

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