PMID- 32169783 OWN - NLM STAT- MEDLINE DCOM- 20210412 LR - 20210412 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 143 DP - 2020 May TI - A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. PG - 1-11 LID - S0169-5002(20)30313-5 [pii] LID - 10.1016/j.lungcan.2020.02.016 [doi] AB - This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) +/- tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du +/- Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design. Both weight-based and fixed dosing of Du and Tr were explored. Du was continued until progression. Tr dosing was finite (up to 6 doses) with increasing dose and/or frequency by DL. 136 patients were enrolled. The majority of drug-related adverse events (AEs) were /=10 %) were colitis/diarrhea, skin, and thyroid dysfunction. Seven patients had DLTs including pneumonitis, myocarditis, diarrhea, encephalitis, motor neuropathy, and enterocolitis. There were 2 treatment-related deaths. Tr and Du exposures did not appear affected by chemotherapy. Among the 73 non-small cell lung cancer (NSCLC) patients treated, the objective response rate was 51 % (95 %CI = 38.7-62.6 %) with a median progression-free and overall survival of 6.5 months (95 % CI = 5.5-9.4 months) and 19.8 months (95 % CI = 14.8 months - not yet reached) respectively. Anti-tumour activity was observed across PD-L1 subtypes. Du 1500 mg q3w and Tr 75 mg q3wx5 can be safely combined with platinum-doublet chemotherapy. Efficacy among NSCLC patients appears comparable to results from other immunotherapy and chemotherapy combination trials. NCT02537418. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Juergens, Rosalyn A AU - Juergens RA AD - Juravinski Cancer Center, McMaster University, Hamilton, ON, Canada. FAU - Hao, Desiree AU - Hao D AD - Tom Baker Cancer Center, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada. FAU - Ellis, Peter M AU - Ellis PM AD - Juravinski Cancer Center, McMaster University, Hamilton, ON, Canada. FAU - Tu, Dongsheng AU - Tu D AD - Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada. FAU - Mates, Mihaela AU - Mates M AD - Cancer Center of Southeastern Ontario, Kingston, Ontario, Canada. FAU - Kollmannsberger, Christian AU - Kollmannsberger C AD - British Columbia Cancer Agency - Vancouver Cancer Center, Vancouver, British Columbia, Canada. FAU - Bradbury, Penelope A AU - Bradbury PA AD - Princess Margaret Cancer Center, Toronto, Ontario, Canada. FAU - Tehfe, Moustapha AU - Tehfe M AD - CHUM Montreal, Quebec, Canada. FAU - Wheatley-Price, Paul AU - Wheatley-Price P AD - The Ottawa Hospital Cancer Centre, Division of Medical Oncology, Ottawa, ON, Canada. FAU - Robinson, Andrew AU - Robinson A AD - Cancer Center of Southeastern Ontario, Kingston, Ontario, Canada. FAU - Bebb, Gwyn AU - Bebb G AD - Tom Baker Cancer Center, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada. FAU - Laskin, Janessa AU - Laskin J AD - British Columbia Cancer Agency - Vancouver Cancer Center, Vancouver, British Columbia, Canada. FAU - Goffin, John AU - Goffin J AD - Juravinski Cancer Center, McMaster University, Hamilton, ON, Canada. FAU - Hilton, John AU - Hilton J AD - The Ottawa Hospital Cancer Centre, Division of Medical Oncology, Ottawa, ON, Canada. FAU - Tomiak, Anna AU - Tomiak A AD - Cancer Center of Southeastern Ontario, Kingston, Ontario, Canada. FAU - Hotte, Sebastien AU - Hotte S AD - Juravinski Cancer Center, McMaster University, Hamilton, ON, Canada. FAU - Goss, Glenwood D AU - Goss GD AD - The Ottawa Hospital Cancer Centre, Division of Medical Oncology, Ottawa, ON, Canada. FAU - Brown-Walker, Pamela AU - Brown-Walker P AD - Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada. FAU - Sun, Xiaoqun AU - Sun X AD - Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada. FAU - Tsao, Ming-Sound AU - Tsao MS AD - Princess Margaret Cancer Center, Toronto, Ontario, Canada. FAU - Cabanero, Michael AU - Cabanero M AD - Princess Margaret Cancer Center, Toronto, Ontario, Canada. FAU - Gauthier, Isabelle AU - Gauthier I AD - Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada. FAU - Song, Xuyang AU - Song X AD - Global Medicines Development, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Dennis, Phillip A AU - Dennis PA AD - Global Medicines Development, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Seymour, Lesley K AU - Seymour LK AD - Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada. Electronic address: lseymour@ctg.queensu.ca. FAU - Smoragiewicz, Martin AU - Smoragiewicz M AD - Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada. FAU - Laurie, Scott A AU - Laurie SA AD - The Ottawa Hospital Cancer Centre, Division of Medical Oncology, Ottawa, ON, Canada. LA - eng SI - ClinicalTrials.gov/NCT02537418 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20200228 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 28X28X9OKV (durvalumab) RN - BG3F62OND5 (Carboplatin) RN - Q20Q21Q62J (Cisplatin) RN - QEN1X95CIX (tremelimumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/administration & dosage MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/administration & dosage MH - Cisplatin/administration & dosage MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Neoplasms/*drug therapy/pathology MH - Prognosis MH - Survival Rate OTO - NOTNLM OT - Durvalumab OT - Immunotherapy OT - Lung cancer OT - Phase I OT - Tremelimumab EDAT- 2020/03/15 06:00 MHDA- 2021/04/13 06:00 CRDT- 2020/03/15 06:00 PHST- 2020/01/02 00:00 [received] PHST- 2020/02/10 00:00 [revised] PHST- 2020/02/22 00:00 [accepted] PHST- 2020/03/15 06:00 [pubmed] PHST- 2021/04/13 06:00 [medline] PHST- 2020/03/15 06:00 [entrez] AID - S0169-5002(20)30313-5 [pii] AID - 10.1016/j.lungcan.2020.02.016 [doi] PST - ppublish SO - Lung Cancer. 2020 May;143:1-11. doi: 10.1016/j.lungcan.2020.02.016. Epub 2020 Feb 28.