A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer.

Autor: Curigliano G; Istituto Europeo di Oncologia, IRCCS, Milano, Italy. giuseppe.curigliano@ieo.it.; University of Milan, Milano, Italy. giuseppe.curigliano@ieo.it., Shapiro GI; Dana-Farber Cancer Institute, Boston, MA, USA., Kristeleit RS; University College London, Cancer Institute, London, UK., Abdul Razak AR; Phase 1 Program, Princess Margaret Cancer Centre, Toronto, ON, Canada., Leong S; University of Colorado Cancer Center, Aurora, CO, USA., Alsina M; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Giordano A; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA., Gelmon KA; BC Cancer, Vancouver, BC, Canada., Stringer-Reasor E; University of Alabama at Birmingham O'Neal Comprehensive Cancer Center, Birmingham, AL, USA., Vaishampayan UN; University of Michigan/Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA., Middleton M; University of Oxford, Oxford, UK., Olszanski AJ; Fox Chase Cancer Center, Philadelphia, PA, USA., Rugo HS; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA., Kern KA; Pfizer, San Diego, CA, USA., Pathan N; Pfizer, San Diego, CA, USA., Perea R; Pfizer, San Diego, CA, USA., Pierce KJ; Pfizer, Groton, CT, USA., Mutka SC; Celcuity, Minneapolis, MD, USA., Wainberg ZA; David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2023 Jan; Vol. 128 (1), pp. 30-41. Date of Electronic Publication: 2022 Nov 05.
DOI: 10.1038/s41416-022-02025-9
Abstrakt: Background: This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours.
Methods: Patients with various malignancies were administered gedatolisib (90‒310 mg intravenously every week [QW]) plus docetaxel (arm A) or cisplatin (arm B) (each 75 mg/m 2 intravenously Q3W) or dacomitinib (30 or 45 mg/day orally). The safety and tolerability of combination therapies were assessed during dose escalation; objective response (OR) and safety were assessed during dose expansion.
Results: Of 110 patients enrolled, 107 received gedatolisib combination treatment. Seven of 70 (10.0%) evaluable patients had dose-limiting toxicities; the most common was grade 3 oral mucositis (n = 3). Based upon reprioritisation of the sponsor's portfolio, dose expansion focused on arm B, gedatolisib (180 mg QW) plus cisplatin in patients (N = 22) with triple-negative breast cancer (TNBC). OR (95% CI) was achieved in four of ten patients in first-line (overall response rate 40.0% [12.2-73.8%]) and four of 12 in second/third-line (33.3% [9.9-65.1%]) settings. One patient in each TNBC arm (10%, first-line; 8.3%, second/third-line) achieved a complete response.
Conclusions: Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC.
Clinical Trial: ClinicalTrial.gov: NCT01920061.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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