PMID- 32020438 OWN - NLM STAT- MEDLINE DCOM- 20210902 LR - 20210902 IS - 1573-0646 (Electronic) IS - 0167-6997 (Linking) VI - 38 IP - 5 DP - 2020 Oct TI - A Canadian cancer trials group phase IB study of durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4) given concurrently or sequentially in patients with advanced, incurable solid malignancies. PG - 1442-1447 LID - 10.1007/s10637-020-00904-7 [doi] AB - Background The IND.226 study was a phase Ib study to determine the recommended phase II dose of durvalumab + tremelimumab in combination with standard platinum-doublet chemotherapy. Sequential administration of multiple agents increases total chair time adding costs overall and inconvenience for patients. This cohort of the IND.226 study evaluated the safety and tolerability of durvalumab + tremelimumab given either sequentially (SEQ) or concurrently (CON). Methods Patients with advanced solid tumours were enrolled and randomised to either SEQ tremelimumab 75 mg IV over 1 h followed by durvalumab 1500 mg IV over 1 h q4wks on the same day, or CON administration over 1 h. The serum pharmacokinetic profile of SEQ versus CON of durvalumab and tremelimumab administration was also evaluated. Results 14 patients either received SEQ (n = 7pts) or CON (n = 7 pts). There were no infusion related reactions. Drug related adverse events (AEs) were mainly low grade and manageable, and comparable in frequency between SEQ/CON- fatigue (43%/57%), rash (43%/43%), pruritus (43%/29%) and nausea (14%/29%). One patient in each cohort discontinued treatment due to toxicity. The PK profiles of durvalumab and tremelimumab were similar between CON and SEQ, and to historical reference data. Conclusions Concurrent administration of durvalumab and tremelimumab over 1 h is safe with a comparable PK profile to sequential administration. FAU - Nehra, J AU - Nehra J AD - Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada. FAU - Bradbury, P A AU - Bradbury PA AD - Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada. FAU - Ellis, P M AU - Ellis PM AD - Department of Oncology - Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Canada. FAU - Laskin, J AU - Laskin J AD - Division of Medical Oncology, BCCA Vancouver Cancer Centre, Vancouver, Canada. FAU - Kollmannsberger, C AU - Kollmannsberger C AD - Division of Medical Oncology, BCCA Vancouver Cancer Centre, Vancouver, Canada. FAU - Hao, D AU - Hao D AD - Department of Oncology - Section of Medical Oncology, Tom Baker Cancer Centre University of Calgary, Calgary, Canada. FAU - Juergens, R A AU - Juergens RA AD - Department of Oncology - Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Canada. FAU - Goss, G AU - Goss G AD - Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Canada. FAU - Wheatley-Price, P AU - Wheatley-Price P AD - Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Canada. FAU - Hotte, S J AU - Hotte SJ AD - Department of Oncology - Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Canada. FAU - Gelmon, K AU - Gelmon K AD - Division of Medical Oncology, BCCA Vancouver Cancer Centre, Vancouver, Canada. FAU - Tinker, A V AU - Tinker AV AD - Division of Medical Oncology, BCCA Vancouver Cancer Centre, Vancouver, Canada. FAU - Brown-Walker, P AU - Brown-Walker P AD - Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada. FAU - Gauthier, I AU - Gauthier I AD - Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada. FAU - Tu, D AU - Tu D AD - Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada. FAU - Song, X AU - Song X AD - Clinical Pharmacology & Safety Sciences, AstraZeneca, Gaithersburg, MD, USA. FAU - Khan, A AU - Khan A AD - Clinical Pharmacology & Safety Sciences, AstraZeneca, Gaithersburg, MD, USA. FAU - Seymour, Lesley AU - Seymour L AD - Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada. lseymour@ctg.queensu.ca. FAU - Smoragiewicz, M AU - Smoragiewicz M AD - Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200204 PL - United States TA - Invest New Drugs JT - Investigational new drugs JID - 8309330 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Immune Checkpoint Inhibitors) RN - 28X28X9OKV (durvalumab) RN - QEN1X95CIX (tremelimumab) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal/*administration & dosage/adverse effects/blood/pharmacokinetics MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects/blood/pharmacokinetics MH - Antineoplastic Agents, Immunological/*administration & dosage/adverse effects/blood/pharmacokinetics MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects/pharmacokinetics MH - Female MH - Humans MH - Immune Checkpoint Inhibitors/*administration & dosage/adverse effects/blood/pharmacokinetics MH - Male MH - Middle Aged MH - Neoplasms/blood/*drug therapy/metabolism OTO - NOTNLM OT - Clinical trial OT - Durvalumab OT - Pharmacokinetics OT - Tremelimumab EDAT- 2020/02/06 06:00 MHDA- 2021/09/03 06:00 CRDT- 2020/02/06 06:00 PHST- 2019/12/12 00:00 [received] PHST- 2020/01/27 00:00 [accepted] PHST- 2020/02/06 06:00 [pubmed] PHST- 2021/09/03 06:00 [medline] PHST- 2020/02/06 06:00 [entrez] AID - 10.1007/s10637-020-00904-7 [pii] AID - 10.1007/s10637-020-00904-7 [doi] PST - ppublish SO - Invest New Drugs. 2020 Oct;38(5):1442-1447. doi: 10.1007/s10637-020-00904-7. Epub 2020 Feb 4.