Palazestrant, a novel oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), in patients with ER+/HER2− advanced or metastatic breast cancer: phase 1/2 study results
Guardat en:
| Publicat a: | Breast Cancer Research vol. 27 (2025), p. 1-16 |
|---|---|
| Autor principal: | |
| Altres autors: | , , , , , , , , , , , , , , |
| Publicat: |
Springer Nature B.V.
|
| Matèries: | |
| Accés en línia: | Citation/Abstract Full Text Full Text - PDF |
| Etiquetes: |
Sense etiquetes, Sigues el primer a etiquetar aquest registre!
|
MARC
| LEADER | 00000nab a2200000uu 4500 | ||
|---|---|---|---|
| 001 | 3227648849 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 1465-5411 | ||
| 022 | |a 1465-542X | ||
| 024 | 7 | |a 10.1186/s13058-025-02049-y |2 doi | |
| 035 | |a 3227648849 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 242930 |2 nlm | ||
| 100 | 1 | |a Hamilton, Erika P | |
| 245 | 1 | |a Palazestrant, a novel oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), in patients with ER+/HER2− advanced or metastatic breast cancer: phase 1/2 study results | |
| 260 | |b Springer Nature B.V. |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a BackgroundEndocrine resistance is a major challenge in treating patients with ER+ /HER2− metastatic breast cancer (MBC) necessitating a switch from endocrine therapy to more toxic therapies. Mutations in ESR1 constitute a key mechanism of resistance to endocrine therapy in ER+ /HER2− BC. Therapies that overcome endocrine resistance are needed. Palazestrant is a novel oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) belonging to a new class of ER-targeting agents that completely blocks estrogen-induced transcriptional activity, regardless of ESR1 mutation status. This first-in-human, open-label, multicenter, phase 1/2 dose-escalation/expansion study was designed to determine the recommended phase 2 dose (RP2D) and to evaluate safety, pharmacokinetics, and antitumor activity of palazestrant in patients with ER+ /HER2− MBC with disease progression on prior treatment.MethodsAdults with ER+ /HER2‒ MBC who received ≥ 1 prior line of endocrine therapy for advanced disease and ≤ 2 prior chemotherapy regimens for metastatic disease were eligible. Patients received once-daily oral palazestrant (30–300 mg) in 28-day cycles until progression or intolerable toxicity.ResultsThis study enrolled 146 patients. No dose-limiting toxicities were observed at doses up to 300 mg/day palazestrant. Confirmed partial responses were observed with 60 and 120 mg/day palazestrant. Both doses showed similar and tolerable safety profiles, favorable pharmacokinetics, and steady-state plasma concentrations above the predicted threshold for complete ER inhibition. Greater clinical benefit at palazestrant 120 mg/day (46%) versus 60 mg/day (19%) led to selection of 120 mg/day as RP2D and study expansion dose. At 120 mg/day, the median progression-free survival was 4.8 months (95% CI, 3.5–7.1) overall and 5.6 months (95% CI, 4.8–NE) among patients with cancers with ESR1 mutations. Most treatment-emergent adverse events (TEAEs) were grade 1–2. The most common TEAEs were nausea (62.8%), vomiting (29.1%), and fatigue (25.6%). The most common grade ≥ 3 TEAE was transient neutropenia (10.5%) managed by dose interruption and reduction.ConclusionsPalazestrant demonstrated a manageable safety profile, with antitumor activity observed in patients with heavily pretreated cancers with wild-type and ESR1-mutated BC. These data support the ongoing phase 3 study evaluating palazestrant in patients with ER+ /HER2 − MBC.Trial registrationClinicalTrials.gov, NCT04505826. Registered August 6, 2020. | |
| 651 | 4 | |a United States--US | |
| 653 | |a Plasma | ||
| 653 | |a Womens health | ||
| 653 | |a Metastasis | ||
| 653 | |a Toxicity | ||
| 653 | |a Cancer therapies | ||
| 653 | |a Mutation | ||
| 653 | |a Antitumor activity | ||
| 653 | |a Laboratories | ||
| 653 | |a Breast cancer | ||
| 653 | |a Metastases | ||
| 653 | |a Estrogens | ||
| 653 | |a Kinases | ||
| 653 | |a Estrogen receptors | ||
| 653 | |a ErbB-2 protein | ||
| 653 | |a Endocrine therapy | ||
| 653 | |a Patients | ||
| 653 | |a Neutropenia | ||
| 653 | |a Pharmacokinetics | ||
| 653 | |a Cyclin-dependent kinases | ||
| 653 | |a Biomarkers | ||
| 653 | |a Chemotherapy | ||
| 653 | |a Tumors | ||
| 653 | |a Cancer | ||
| 700 | 1 | |a Patel, Manish R | |
| 700 | 1 | |a Borges, Virginia F | |
| 700 | 1 | |a Meisel, Jane L | |
| 700 | 1 | |a Okera, Meena | |
| 700 | 1 | |a Alemany, Carlos A | |
| 700 | 1 | |a Pluard, Timothy J | |
| 700 | 1 | |a Wesolowski, Robert | |
| 700 | 1 | |a Sabanathan, Dhanusha | |
| 700 | 1 | |a Miller, Kathy D | |
| 700 | 1 | |a Conlin, Alison K | |
| 700 | 1 | |a McCarthy, Nicole | |
| 700 | 1 | |a Shaw, Morena | |
| 700 | 1 | |a Tonda, Margaret | |
| 700 | 1 | |a Shilkrut, Mark | |
| 700 | 1 | |a Lin, Nancy U | |
| 773 | 0 | |t Breast Cancer Research |g vol. 27 (2025), p. 1-16 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3227648849/abstract/embedded/J7RWLIQ9I3C9JK51?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3227648849/fulltext/embedded/J7RWLIQ9I3C9JK51?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3227648849/fulltextPDF/embedded/J7RWLIQ9I3C9JK51?source=fedsrch |