First-in-human phase 1/2a study of the first-in-class, next-generation CDK4-selective inhibitor PF-07220060 + endocrine therapy (ET): Updated safety data in patients with HR+/HER2− mBC.
Rattachement africain : us, gb, mx, cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
3108 Background: PF-07220060 is a novel, highly selective CDK4 inhibitor with significant CDK6 sparing. Preliminary data have been reported for the monotherapy dose-escalation cohort (Part 1A) and ET combination dose-finding cohorts (Parts 1B-C) in the first-in-human study of PF-07220060 in patients (pts) with advanced solid tumors (1). Herein, we report updated safety data for PF-07220060 + ET in pts with HR+/HER2− advanced/metastatic breast cancer (mBC), including extended follow-up data for pts in dose-finding cohorts (Parts 1B-C) and first disclosure of data for pts in dose-expansion cohorts (Parts 2B-C). Methods: In Parts 1B and 1C of this Phase 1/2a study (NCT04557449),PF-07220060 + ET (letrozole [LET] or fulvestrant [FUL], respectively) was administered to pts with HR+/HER2− mBC as ≥2L therapy after prior CDK4/6 inhibitors (CDK4/6i). In dose-expansion cohort 2B, pts with HR+/HER2− mBC received 1L PF-07220060 + LET; in Part 2C, pts with progression after prior ET received PF-07220060 + FUL. Pts in Parts 2B-C were CDK4/6i-naïve. Primary objective was to evaluate safety and tolerability of PF-07220060 + ET. Results: At data cutoff (Nov 1, 2023), 33 pts received PF-07220060 (300 or 400 mg BID) + ET in Parts 1B-C; 34 pts in Part 2B and 36 pts in Part 2C received PF-07220060 (300 mg BID) with LET or FUL, respectively. Table summarizes patient characteristics in each cohort. In the pooled 1B-C cohort, the most common TEAEs were neutropenia (54.5% [18.2% G3]), diarrhea (42.4% [0% G3]), and nausea (42.4% [3.0% G3]). In Parts 2B-C, the most common TEAEs were neutropenia (61.8%/36.1% [23.5%/11.1% G3]), leukopenia (38.2%/33.3% [0%/13.9% G3]), and anemia (23.5%/27.8% [0%/2.8% G3]). No >G3 TEAEs were reported in Parts 1B-C or 2B-C. In Parts 1B-C, 2B, and 2C, TEAEs leading to discontinuation were reported in 3.0%, 5.9%, and 8.3% of pts, respectively; dose reductions due to AEs were reported in 12.1%, 5.9%, and 8.3% of pts, respectively. Median (range) relative dose intensity (RDI) of PF-07220060 was 98.3% (52.5–100) in Parts 1B-C, 99.8% (37.2–100) in Part 2B, and 99.7% (68.6–100) in Part 2C. Conclusions: PF-07220060 + ET was well tolerated in pts with HR+/HER2− mBC across post-CDK4/6i and CDK4/6i-naïve cohorts. Incidence of G3 neutropenia and other TEAEs was low, enabling high RDI and potential for continuous target coverage. 1. Yap, et al. J Clin Oncol. 2023;41(16_suppl):3009. Clinical trial information: NCT04557449 . [Table: see text]
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- First-in-human phase 1/2a study of the first-in-class, next-generation CDK4-selective inhibitor PF-07220060 + endocrine therapy (ET): Updated safety data in patients with HR+/HER2− mBC.
- Date Crossref
- 01/06/2024
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Dana-Farber Cancer Institute pays non établi dans la noticeStructure de recherche
-
South Texas Accelerated Research Therapeutics pays non établi dans la noticeStructure de recherche
-
Start Treatment & Recovery Centers pays non établi dans la noticeÉtablissement de santé
-
Sarah Cannon Research Institute pays non établi dans la noticeUniversité ou école supérieure
-
Queen Mary University of London Barts Cancer Institute pays non établi dans la noticeUniversité ou école supérieure
-
Barts Cancer Institute pays non établi dans la noticeUniversité ou école supérieure
-
Instituto Nacional de Cancerología pays non établi dans la noticeOrganisme public
-
Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
-
Henan Cancer Hospital Department of Breast pays non établi dans la noticeÉtablissement de santé
-
University of Manchester pays non établi dans la noticeUniversité ou école supérieure
-
The Christie NHS Foundation Trust pays non établi dans la noticeOrganisme public
-
Sarah Cannon pays non établi dans la noticeStructure de recherche
Dana-Farber Cancer Institute, South Texas Accelerated Research Therapeutics et Start Treatment & Recovery Centers, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.