{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["128(1)"],"submitter":["Curigliano G"],"funding":["Pfizer"],"pubmed_abstract":["<h4>Background</h4>This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours.<h4>Methods</h4>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<sup>2</sup> 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.<h4>Results</h4>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.<h4>Conclusions</h4>Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC.<h4>Clinical trial</h4>ClinicalTrial.gov: NCT01920061."],"journal":["British journal of cancer"],"pagination":["30-41"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9814742"],"repository":["biostudies-literature"],"pubmed_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."],"pmcid":["PMC9814742"],"pubmed_authors":["Leong S","Middleton M","Kristeleit RS","Abdul Razak AR","Giordano A","Alsina M","Rugo HS","Stringer-Reasor E","Kern KA","Perea R","Pierce KJ","Shapiro GI","Vaishampayan UN","Olszanski AJ","Wainberg ZA","Pathan N","Curigliano G","Mutka SC","Gelmon KA"],"additional_accession":[]},"is_claimable":false,"name":"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.","description":"<h4>Background</h4>This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours.<h4>Methods</h4>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<sup>2</sup> 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.<h4>Results</h4>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.<h4>Conclusions</h4>Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC.<h4>Clinical trial</h4>ClinicalTrial.gov: NCT01920061.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-28T01:53:30.826Z","creation":"2025-05-29T16:36:20.229Z"},"accession":"S-EPMC9814742","cross_references":{"pubmed":["36335217"],"doi":["10.1038/s41416-022-02025-9"]}}