NCT05508906

Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, Everolimus, or Atirmociclib in ER+, HER2- Breast Cancer

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 190 (estimated)
• Sponsor: Olema Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1b open-label, 2-part study in 3 treatment groups. The 3 treatment groups are as follows: Treatment Group 1: Palazestrant (OP-1250) in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation). Treatment Group 2: Palazestrant (OP-1250) in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation). Treatment Group 3: Palazestrant (OP-1250) in combination with everolimus. Treatment Group 4: Palazestrant (OP-1250) in combination with atirmociclib.

Detailed description

Part 1 (Dose Escalation): This part will evaluate the safety and pharmacokinetics of a range of doses of palazestrant administered orally (PO) daily to subjects in combination with 600 mg of ribociclib administered PO daily for 21 consecutive days followed by 7 days off treatment (Treatment Group 1) or with 300 mg or 250 mg of alpelisib administered PO daily (Treatment Group 2) or with everolimus 10 mg administered PO daily (Treatment Group 3) and determine the RP2D (Recommended Phase 2 Dose) for each treatment group. Part 1, for Treatment Group 4, will evaluate the safety and pharmacokinetics of OP-1250 at 60 mg or 90 mg doses administered orally (PO) QD in combination with atirmociclib 300 mg PO twice a day (BID). Part 2 (Dose Expansion): This part of the study will further evaluate the safety and PK of palazestrant at the RP2D in combination with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3) and provide an exploratory estimate of anti-tumor activity of the combinations. An additional group of palazestrant at an alternate dose level in combination with ribociclib (Treatment Group 1b) will be explored to optimize the RP2D of palazestrant. Part 2, for Treatment Group 4, will further evaluate the safety and pharmacokinetics of atirmociclib and OP-1250 at the recommended dose for expansion.

Conditions

• Metastatic Breast Cancer
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• Breast Cancer
• Locally Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Palazestrant	Complete estrogen receptor antagonist (CERAN)
DRUG	Ribociclib	All subjects in Treatment Group 1 will receive palazestrant in combination with ribociclib.
DRUG	Alpelisib	All subjects in Treatment Group 2 will receive palazestrant in combination with alpelisib.
DRUG	Everolimus	All subjects in Treatment Group 3 will receive palazestrant in combination with everolimus.
DRUG	Atirmociclib	All subjects in Treatment Group 4 will receive palazestrant in combination with atirmociclib.

Timeline

• Start date: 2022-08-31
• Primary completion: 2027-12-31
• Completion: 2028-01-31
• First posted: 2022-08-19
• Last updated: 2025-10-22

Locations

16 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study