A Canadian cancer trials group phase IB study of durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4) given concurren
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PHASE I STUDIES
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 J. Nehra 1 & P. A. Bradbury 2 & P. M. Ellis 3 & J. Laskin 4 & C. Kollmannsberger 4 & D. Hao 5 & R. A. Juergens 3 & G. Goss 6 & P. Wheatley-Price 6 & S. J. Hotte 3 & K. Gelmon 4 & A. V. Tinker 4 & P. Brown-Walker 1 & I. Gauthier 1 & D. Tu 1 & X. Song 7 & A. Khan 7 & Lesley Seymour 1 & M. Smoragiewicz 1 Received: 12 December 2019 / Accepted: 27 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary 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 The PK profiles of durvalumab and tremelimumab were similar between CON and SEQ, and to historical reference data.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. Keywords Clinical trial . Durvalumab . Tremelimumab . Pharmacokinetics
* Lesley Seymour [email protected] 1
Canadian Cancer Trials Group, Queen’s University, 10 Stuart Street, Kingston, ON K7L3N6, Canada
2
Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada
3
Department of Oncology - Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Canada
4
Division of Medical Oncology, BCCA Vancouver Cancer Centre, Vancouver, Canada
5
Department of Oncology - Section of Medical Oncology, Tom Baker Cancer Centre University of Calgary, Calgary, Canada
6
Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Canada
7
Clinical Pharmacology & Safety Sciences, AstraZeneca, Gaithersburg, MD, USA
Introduction Immune checkpoint inhibitors (ICI) targeting the pathways PD-(L)1 or CTLA-4 have been approved as monotherapy for the treatment of multiple cancer types [1–5]. Although responses can be deep and durable to monoth
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