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

Sponsor

Olema Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04505826

Collaborator

(none)

Enrollment

Locations

Arms

39.6

Anticipated Duration (Months)

10.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial is a Phase 1-2, open-label, multi-center, dose-escalation and expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of OP-1250.

Condition or Disease	Intervention/Treatment	Phase
Hormone Receptor Positive Breast Carcinoma HER2-negative Breast Cancer	Drug: OP-1250	Phase 1/Phase 2

Detailed Description

OP-1250 is a small molecule Complete Estrogen Receptor ANtagonist (CERAN). OP-1250 potently competes with the endogenous activating estrogenic ligand 17-beta estradiol for binding in the ligand binding pocket. OP-1250 blocks estrogen-driven transcriptional activity, inhibits estrogen-driven breast cancer cell growth, and induces degradation of the estrogen receptor.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

94 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Open-label, First-in-Human, Multicenter, Dose Escalation and Dose Expansion Study of OP-1250 Monotherapy in Adult Subjects With Advanced and/or Metastatic Hormone Receptor (HR)-Positive, HER2-negative Breast Cancer

Actual Study Start Date :

Aug 13, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OP-1250 Dose Escalation This portion of the study will evaluate the safety and pharmacology of a range of OP-1250 doses administered daily in subjects with advanced and/or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer and to determine the RP2D	Drug: OP-1250 Complete Estrogen Receptor ANtagonist (CERAN)
Experimental: OP-1250 Expansion This portion of the study further explores the clinical activity, safety and pharmacology of OP-1250 monotherapy at the RP2D and to estimate preliminary data of anti-tumor efficacy	Drug: OP-1250 Complete Estrogen Receptor ANtagonist (CERAN)

Arm

Intervention/Treatment

Experimental: OP-1250 Dose Escalation

This portion of the study will evaluate the safety and pharmacology of a range of OP-1250 doses administered daily in subjects with advanced and/or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer and to determine the RP2D

Drug: OP-1250

Complete Estrogen Receptor ANtagonist (CERAN)

Experimental: OP-1250 Expansion

This portion of the study further explores the clinical activity, safety and pharmacology of OP-1250 monotherapy at the RP2D and to estimate preliminary data of anti-tumor efficacy

Drug: OP-1250

Complete Estrogen Receptor ANtagonist (CERAN)

Outcome Measures

Primary Outcome Measures

Determine MTD and/or RP2D of OP-1250 when used as a single agent [Up to one year]
Number of patients with DLT as defined in the protocol

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Must not have received prior oral endocrine therapy > 2 weeks prior to first dose
Must not have received prior fulvestrant, chemotherapy, antibody therapy, or investigational therapy ≤ 4 weeks 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advent Health	Orlando	Florida	United States	32804
2	Florida Cancer Center	Sarasota	Florida	United States	34232
3	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239
4	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
5	Macquarie University	Sydney	New South Wales	Australia	2109
6	Westmead	Westmead	New South Wales	Australia	2145
7	ICON Cancer Centre	Auchenflower	Queensland	Australia	4066
8	Cancer Research South Australia	Adelaide	South Australia	Australia	5000
9	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000

Sponsors and Collaborators

Olema Pharmaceuticals, Inc.

Investigators

Study Director: Jo Anne Zujewski, MD, Olema Pharmaceuticals, Inc.
Study Director: Trinh Le, Olema Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Olema Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT04505826

Other Study ID Numbers:

OP-1250-001

First Posted:

Aug 10, 2020

Last Update Posted:

Oct 25, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of Oct 25, 2021