Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Palazestrant
OP-1250 · 5 trials · 9 indications
To compare PFS, based on a local investigator assessment, between investigational (palazestrant with ribociclib + letrozole-matching placebo) and control (letrozole with ribociclib + palazestrant-matching placebo) arms.
To evaluate the number of participants with adverse events
To evaluate the number of participants reducing the dose of palazestrant
To evaluate the number of participants discontinuing palazestrant
To compare PFS, based on a Blinded Independent Review Committee (BIRC) assessment, between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1-mutation detected and ESR1-mutation not detected participants.
To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and/ or recommended dose expansion (RDE) of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4). The incidence of DLTs will be assessed in the Dose Escalation part (Part 1) of the study.
Characterize the incidence, nature and severity of TEAEs and SAEs of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4) according to NCI-CTCAE version 5.0.
To assess the PK of palazestrant (and potential metabolites) in combination with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4). Plasma levels of palazestrant will be assessed at predefined intervals to establish PK parameters (including: Cmax, Cmin, Tmax, AUC, and t1⁄2 as data permit) and palazestrant trough concentration at steady state).
Number of Participants with Dose Limiting Toxicities (DLT) during Dose Escalation Only
Characterize the incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250 in patients that had at least one treatment emergent adverse event according to NCI-CTCAE version 5.0.
Plasma concentrations of OP-1250 assessed steady state
Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines (Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR)). Overall response rate which includes confirmed Partial Response (cPR).
| Arm | Type | Description |
|---|---|---|
| Palazestrant | EXPERIMENTAL | Participants will receive palazestrant, ribociclib and letrozole-matching placebo |
| Letrozole | ACTIVE_COMPARATOR | Participants will receive letrozole, ribociclib and palazestrant-matching placebo |
| Palazestrant (OP-1250) | EXPERIMENTAL | Participants will receive Palazestrant |
| Standard of Care Endocrine Therapy | ACTIVE_COMPARATOR | Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane) |
| Palazestrant with Ribociclib | EXPERIMENTAL | Treatment Group 1: Palazestrant in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation). |
| Palazestrant with Alpelisib | EXPERIMENTAL | Treatment Group 2: Palazestrant in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation) |
| Palazestrant with Everolimus | EXPERIMENTAL | Treatment Group 3: Palazestrant in combination with everolimus |
| Palazestrant with Atirmociclib | EXPERIMENTAL | Treatment Group 4: Palazestrant in combination with atirmociclib |
| Dose Escalation | EXPERIMENTAL | This portion of the study will evaluate the safety and pharmacology of a range of OP-1250 doses administered daily with Palbociclib in subjects with advanced and/or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer |
| Dose Expansion | EXPERIMENTAL | This portion of the study further explores the clinical activity, safety and pharmacology of OP-1250 in combination with Palbociclib and estimates preliminary data of anti-tumor efficacy |
| OP-1250 Phase I Part A (Dose Escalation) | EXPERIMENTAL | Phase I Part A will evaluate the safety and pharmacokinetics (PK)of a range of OP-1250 doses to identify the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D). |
| OP-1250 Phase I Part B (Dose Expansion) | EXPERIMENTAL | Phase I Part B will evaluate the safety and PK of OP-1250 to confirm the RP2D dose. |
| OP-1250 Phase II | EXPERIMENTAL | This portion of the study further explores the clinical activity, safety, and PK of OP-1250 monotherapy at the RP2D and will estimate preliminary anti-tumor efficacy in 3 cohorts. Cohort A will enroll subjects with measurable disease without evidence of Central Nervous System (CNS) metastases; Cohort B will enroll subjects with non-measurable (evaluable) disease without evidence of CNS metastases; and Cohort C will enroll subjects with evaluable disease (measurable and non-measurable) with CNS metastases. |
| Name | Type | Description |
|---|---|---|
| Palazestrant | DRUG | Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle. |
| Letrozole-matching placebo | DRUG | Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle |
| Ribociclib | DRUG | Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle. |
| Letrozole | DRUG | Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle |
| Palazestrant matching-placebo | DRUG | Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle |
| Fulvestrant | DRUG | Participants will be treated with fulvestrant on C1D1, C1D15, and then on Day 1 of every subsequent 4 week (28 day) cycle |
| Anastrozole | DRUG | Participants will be treated with anastrozole once daily on a 4 week (28 day) cycle |
| Exemestane | DRUG | Participants will be treated with exemestane once daily on a 4 week (28 day) cycle |
| Alpelisib | DRUG | All subjects in Treatment Group 2 will receive palazestrant in combination with alpelisib. |
| Everolimus | DRUG | All subjects in Treatment Group 3 will receive palazestrant in combination with everolimus. |
| Atirmociclib | DRUG | All subjects in Treatment Group 4 will receive palazestrant in combination with atirmociclib. |
| Palbociclib | DRUG | Palbociclib is an approved CDK 4/6 Inhibitor drug |
| OP-1250 | DRUG | Complete Estrogen Receptor ANtagonist (CERAN) |
Inclusion Criteria: * Adult female or male participants. * ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy. * Evaluable disease (measurable disease per RECIST 1.1 or bone-only disease). * De novo advanced breast cancer or with disease recurrence occu...
OP-1250 is being developed for the treatment of hormone receptor positive, HER2-negative breast cancer, including advanced and metastatic disease. It is an oral small molecule under investigation in patients with these tumor types. The clinical program enrolled adults with HR+, HER2- breast cancer in the United States and Australia.
OP-1250 targets the estrogen receptor. It is a small molecule designed to act on this receptor, which drives tumor growth in hormone receptor positive breast cancer. Because the trial selected patients by biomarker, the estrogen receptor status of participants was relevant to enrollment in the study.
OP-1250 is being developed by Olema Pharmaceuticals, Inc., which trades under the ticker OLMA. The company is the sponsor of the clinical program evaluating the drug in hormone receptor positive, HER2-negative breast cancer.
OP-1250 is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA. The Phase 1 program has been completed, with no trials currently listed as active.
OP-1250 was studied in NCT04505826, a Phase 1 dose escalation and expansion study in subjects with advanced and/or metastatic HR+, HER2- breast cancer. The trial enrolled 153 participants, was controlled, and was conducted in the United States and Australia. It is listed as completed.
NCT04505826 enrolled adults 18 years and older of any sex with hormone receptor positive, HER2-negative breast cancer. Participants had advanced and/or metastatic disease, and enrollment was biomarker selected. The study was not randomized and was not double blinded, and it did not include healthy volunteers.