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- Title
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.
- Authors
Curigliano, Giuseppe; Shapiro, Geoffrey I.; Kristeleit, Rebecca S.; Abdul Razak, Albiruni R.; Leong, Stephen; Alsina, Maria; Giordano, Antonio; Gelmon, Karen A.; Stringer-Reasor, Erica; Vaishampayan, Ulka N.; Middleton, Mark; Olszanski, Anthony J.; Rugo, Hope S.; Kern, Kenneth A.; Pathan, Nuzhat; Perea, Rachelle; Pierce, Kristen J.; Mutka, Sarah C.; Wainberg, Zev A.
- Abstract
<bold>Background: </bold>This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours.<bold>Methods: </bold>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/m2 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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC.<bold>Clinical Trial: </bold>ClinicalTrial.gov: NCT01920061.
- Publication
British Journal of Cancer, 2023, Vol 128, Issue 1, p30
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-022-02025-9