Pharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy

摘要: Abstract Background In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), anti-CTLA-4 in combination with one four standard platinum-doublet chemotherapy regimens. We will present update overall survival data. Methods Regardless tumour PD-L1 status, patients were enrolled into cohorts: pemetrexed, gemcitabine, etoposide (each cisplatin or carboplatin) nab-paclitaxel (with carboplatin), each which evaluated six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment cohorts was allowed. Limited PK collected ≤1 hour pre-dose ≤10 minutes post-dose on day 1 cycles 1-3 as well week 6 8 post chemotherapy. Results One hundred thirty-six (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority had non-small cell (53.7%) small (13.2%) lung cancer. Immune-related adverse events (irAEs) that considered related D T mainly Table . 474P Level Durvalumab Q3W Tremelimumab chemotherapy) (after 0 15mg/kg - 1 mg/kg X 1-2 doses 2a 3 Q6w 2b 3 mg/kg 1125mg 56 mg 4 Q3w 2 1500mg 75 mg Conclusions Standard regimens did not alter D+T compared historical monotherapy therapy Toxicities manageable associated PK. Clinical trial identification NCT02537418. Legal entity responsible for study Canadian Cancer Trials Group (CCTG). Funding AstraZeneca provided drug partial funding support (CCTG) study. Disclosure D. Hao: Honoraria (self), Advisory Board: Roche; Board; clinical trial: BMS; Research grant / (institution), AstraZeneca; Merck; BI. P.M. Ellis: Consultancy, Takeda; Abbvie; (self): Pfizer; BMS. R.A. Juergens: Consultancy: Pfizer. P.A. Bradbury: Lilly; M. Tsao: (institution): Merck. Tehfe: Speaker Bureau Expert testimony: Celegen; Taiho; Takeda. C.K. Kollmannsberger: Travel Accommodation Expenses: Eisai; Ipsen; Astellas; Janssen; Sanofi. J.R. Goffin: testimony, 2014, 2018: Amgen; 2015: Boehringer Ingelheim; Bristol-Myers Squibb; Expenses, 2017: AstraZeneca. P. Wheatley-Price: Roche. J. Hilton: Novartis; Puma; Eli Lilly. L.K. Seymour: Shareholder Stockholder Stock options, Received behalf CCTG from study: All other authors have declared no conflicts interest.