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Also known as OP-1250
Palazestrant · 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...
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Palazestrant is an investigational oral therapy being developed for breast cancer, including locally advanced and metastatic breast cancer. It is being studied in ER-positive, HER2-negative disease, both as a single agent and in combination with other targeted therapies such as ribociclib, palbociclib, alpelisib, everolimus, and atirmociclib.
Palazestrant targets the estrogen receptor (ER). It belongs to the -estrant class, also known as selective estrogen receptor degraders (SERDs), a class of small molecules designed to bind the estrogen receptor and degrade it. This mechanism is relevant in ER-positive breast cancers, which depend on estrogen receptor signaling for growth.
Palazestrant is being developed by Olema Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker OLMA. The company is running a Phase 3 clinical program evaluating palazestrant in ER-positive, HER2-negative advanced breast cancer, including a first-line combination study and a study versus standard of care.
Palazestrant is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. The Phase 3 program includes a first-line combination trial with ribociclib and a trial comparing palazestrant against standard of care in ER-positive, HER2-negative advanced breast cancer.
Palazestrant is being studied in several trials, including NCT07085767, a Phase 3 trial combining palazestrant with ribociclib for first-line ER-positive, HER2-negative advanced breast cancer; NCT06016738, a Phase 3 trial of palazestrant versus standard of care; and Phase 1 combination studies NCT05508906 and NCT05266105.
Yes, palazestrant is also known as OP-1250. Both names refer to the same investigational oral small molecule developed by Olema Pharmaceuticals. Clinical trial records and publications may use either name, so searches for OP-1250 and palazestrant refer to the same drug candidate.