474P - Pharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy

Abstract

BackgroundIn this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present the PK, and update overall survival data. MethodsRegardless of tumour PD-L1 status, patients were enrolled into one of four cohorts: pemetrexed, gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin), each of which were evaluated in one of six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment of cohorts was allowed. Limited PK was collected ≤1hour pre-dose and ≤10minutes post-dose on day 1 of cycles 1-3 as well as week 6 or 8 post chemotherapy. ResultsOne hundred and thirty-six patients (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority of patients had non-small cell (53.7%) or small cell (13.2%) lung cancer. Immune-related adverse events (irAEs) that were considered related to D or T were mainly </=Grade 2, the most common of which were skin (38%), diarrhea/colitis (29%), and hypothyroidism (18%). Cmax and Ctrough increased in a dose-proportional manner over the dose range of 1 to 3mg/kg for tremelimumab Q3W. PK exposures for both durvalumab at 15mg/kg, 1125mg, or 1500mg Q3W and tremelimumab at 1, 3mg/kg, 56, and 75mg demonstrated accumulation after the administration of multiple doses. PK parameters did not appear to differ across platinum-doublets. After a median follow-up of 19.6 months, 19 patients continued on protocol therapy. Survival data will be updated prior to the meeting. TableTable474PTableDose LevelDurvalumab Q3WTremelimumab (with chemotherapy)Tremelimumab (after chemotherapy)015mg/kg--115mg/kg1mg/kg X 11-2 doses2a15mg/kg1mg/kg X 3 Q6w1-2 doses2b15mg/kg3mg/kg X 11-2 doses Q6w31125mg56mg X 4 Q3w56mg X 2 Q3w41500mg75mg X 4 Q3w75mg X 1 ConclusionsStandard platinum-doublet chemotherapy regimens did not alter the PK of D+T or D compared with historical monotherapy therapy data. Toxicities were manageable and were not associated with PK. Clinical trial identificationNCT02537418. Legal entity responsible for the studyCanadian Cancer Trials Group (CCTG). FundingAstraZeneca provided drug and partial funding to support of this Canadian Cancer Trials Group (CCTG) study. DisclosureD. Hao: Honoraria (self), Advisory Board: Roche; Honoraria (self), Advisory Board; funding for clinical trial: BMS; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: Merck; Honoraria (self), Advisory Board: BI. P.M. Ellis: Honoraria (self), Advisory / Consultancy, Advisory Board: AstraZeneca; Advisory / Consultancy, Advisory Board: Takeda; Honoraria (self), Advisory / Consultancy, Advisory Board: Abbvie; Honoraria (self): Pfizer; Honoraria (self): BMS. R.A. Juergens: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer. P.A. Bradbury: Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (self): Pfizer; Honoraria (self): Lilly; Advisory / Consultancy: BI. M. Tsao: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck. M. Tehfe: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celegen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.K. Kollmannsberger: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Sanofi. J.R. Goffin: Honoraria (self), Speaker Bureau / Expert testimony, 2014, 2018: Amgen; Honoraria (self), 2015: Boehringer Ingelheim; Honoraria (self), 2015: Bristol-Myers Squibb; Honoraria (self), 2018: Merck; Travel / Accommodation / Expenses, 2017: AstraZeneca. P. Wheatley-Price: Advisory / Consultancy: Takeda; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Abbvie; Advisory / Consultancy: Roche. J. Hilton: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Puma; Advisory / Consultancy: Eli Lilly. L.K. Seymour: Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Received funding on behalf of CCTG from AstraZeneca to support the study: AstraZeneca. All other authors have declared no conflicts of interest.