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 The PK profiles of durvalumab and tremelimumab were similar between CON and SEQ, and to historical reference data.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.
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This trial was sponsored and supported by the Canadian Clinical Trials Group. AstraZeneca Pharmaceuticals provided drug and partial funding support.
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Dr. J. Nehra: No conflicts of interest.
Dr. P.A. Bradbury – Honoraria: Abbvie, Pfizer, Lilly, Merck. Advisory boards- Abbvie, BI.
Dr. P.M. Ellis- Advisory Boards: AstraZeneca, Abbvie, Takeda, Pfizer. Honoraria for speaking for: AstraZeneca, Abbvie, Pfizer, Bristol-Myers Squibb.
Dr. J. Laskin: honoraria/ad boards from Roche, BI, Takeda and AstraZeneca. My institution has received research funding from Roche, and AstraZeneca.
Dr. C. Kollmannsberger – No conflicts of interest.
Dr. D. Hao – Advisory Boards: AstraZeneca, Roche, Merck, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly.
Dr. R.A. Juergens – Advisory board, honoraria and grants: AstraZeneca, Bristol-Myers Squibb, Merck. Advisory board and honoraria: Amgen, Boehringer Ingelheim, Novartis, Roche, Pfizer, and Takeda.
Dr. G. D. Goss reports Honoraria: AstraZeneca, BMS, IO Biotech. Travel reimbursement: Boehringer Ingelheim.
Dr. P. Wheatley-Price – Advisory Boards: Takeda, Bristol-Myers Squibb, AstraZeneca, Merck, Abbvie, Roche.
Dr. S. Hotte: Astra Zeneca: Research Funding (institution); honoraria/Advisory boards.
Dr. K. Gelmon: Pharmaceutical Company Associations. Advisory Boards – AstraZeneca, Roche, Novartis, Pfizer, Oncotheryon, Nanostring, Merck, Mylan, Lilly, Genomic Health, Nanostring, BMS. Research Funding – Pfizer, Roche, AstraZeneca, Novartis, BMS. Expert Testimony - Genentech.
Dr. A.V. Tinker: No conflicts of interest.
Dr. P. Brown-Walker – No conflicts of interest.
I. Gauthier: No conflicts of interest.
Dr. D. Tu – No conflicts of interest.
Dr. X. Song – Employee of AstraZeneca and owns stock in AstraZeneca.
A. Khan: Employee of AstraZeneca and owns stock in AstraZeneca.
Dr. L. Seymour – Received funds from AstraZeneca Pharmaceuticals on behalf of CCTG to support the conduct of the trial. Owns stock in AstraZeneca.
Dr. M. Smoragiewicz – No conflicts of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Nehra, J., Bradbury, P.A., Ellis, P.M. et al. 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. Invest New Drugs 38, 1442–1447 (2020). https://doi.org/10.1007/s10637-020-00904-7
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DOI: https://doi.org/10.1007/s10637-020-00904-7