Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors

Annals of Oncology : Official Journal of the European Society for Medical Oncology
X ZhaoShruti Agrawal

Abstract

Nivolumab 3 mg/kg every 2 weeks (Q2W) has shown benefit versus the standard of care in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, flat dosing is expected to shorten preparation time and improve ease of administration. With knowledge of nivolumab safety, efficacy, and pharmacokinetics across a wide dose range in body weight (BW) dosing, assessment of the benefit-risk profile of a 240-mg flat dose relative to the approved 3-mg/kg dose was approached by quantitative clinical pharmacology. A flat dose of 240 mg was selected based on its equivalence to the 3-mg/kg dose at the median BW of ∼80 kg in patients in the nivolumab program. The benefit-risk profile of nivolumab 240 mg was evaluated by comparing exposures at 3 mg/kg Q2W and 240 mg Q2W across BW and tumor types; clinical safety at 3 mg/kg Q2W by BW and exposure quartiles in melanoma, NSCLC, and RCC; and safety and efficacy at 240 mg Q2W relative to 3 mg/kg Q2W in melanoma, NSCLC, and RCC. The median nivolumab exposure and its distribution at 240 mg Q2W were similar to 3 mg/kg Q2W in the simulated population. Safety analyses did not demonstrate a clinically meaningful relationship between BW or nivolumab exposure quartiles and freque...Continue Reading

References

Jan 20, 2012·Clinical Pharmacokinetics·Shuang BaiMark J Dresser
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertPaolo A Ascierto
Jun 2, 2015·The New England Journal of Medicine·Julie BrahmerDavid R Spigel
Sep 26, 2015·The New England Journal of Medicine·Robert J MotzerUNKNOWN CheckMate 025 Investigators
Sep 29, 2015·The New England Journal of Medicine·Hossein BorghaeiJulie R Brahmer
Jul 12, 2016·Human Vaccines & Immunotherapeutics·Gerry KwokYok-Lam Kwong
Oct 11, 2016·The New England Journal of Medicine·Robert L FerrisMaura L Gillison
Nov 24, 2016·Journal for Immunotherapy of Cancer·Shruti AgrawalBrian Lestini
Dec 27, 2016·CPT: Pharmacometrics & Systems Pharmacology·G BajajY Feng

❮ Previous
Next ❯

Citations

Feb 15, 2018·Cancer Chemotherapy and Pharmacology·David WaterhouseNivedita Aanur
Aug 24, 2017·The Annals of Pharmacotherapy·Morgan E Gwynn, David L DeRemer
Jan 13, 2018·Future Oncology·Fabio GomesPaul Lorigan
Feb 21, 2018·Future Oncology·Malmaruha Arasaratnam, Howard Gurney
May 25, 2018·Expert Review of Anticancer Therapy·Kortnye Maureen Smith, Jayesh Desai
Jun 27, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M Ochoa de OlzaE Garralda
Aug 28, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark J Ratain, Daniel A Goldstein
Sep 15, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G V LongX Zhao
Feb 2, 2019·Clinical Pharmacology in Drug Development·Ken Ogasawara, G Caleb Alexander
Mar 1, 2019·Clinical Pharmacokinetics·Maddalena CentanniJ G Coen van Hasselt
Feb 16, 2018·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·V DamuzzoA C Palozzo
May 30, 2019·British Journal of Clinical Pharmacology·Gaurav BajajManish Gupta
Apr 9, 2019·Journal of the National Comprehensive Cancer Network : JNCCN·Daniel G CoitAnita M Engh
Aug 10, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pier Luigi ZinzaniAlison J Moskowitz
Sep 26, 2019·Clinical Pharmacology and Therapeutics·Ana M NovakovicAkash Khandelwal
Dec 28, 2019·Cancers·Sarah L PicardoAaron R Hansen
Jul 30, 2017·The Oncologist·Jeroen J M A HendrikxJos H Beijnen
Jan 20, 2020·Clinical Pharmacology and Therapeutics·Yulia VugmeysterAkash Khandelwal
Apr 24, 2020·British Journal of Clinical Pharmacology·Yara AbdouMarc S Ernstoff
May 20, 2020·British Journal of Clinical Pharmacology·Cody J PeerMark J Ratain
Jun 18, 2020·Journal of Clinical Medicine·Clara Mihaela IonescuDirk Verellen
Apr 22, 2020·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Justine ClarenneFlorian Slimano
Feb 28, 2019·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Mário L de LemosSally Waignein
Mar 15, 2019·Clinical Pharmacokinetics·Hannah Yejin KimAlan V Boddy
Jul 7, 2019·Advances in Therapy·Justin J WilkinsAkash Khandelwal
Jun 12, 2019·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Jacopo GiulianiAndrea Bonetti
May 21, 2019·The Tohoku Journal of Experimental Medicine·Ken SaijoChikashi Ishioka
Mar 5, 2020·Therapeutic Advances in Medical Oncology·Fausto Meriggi, Alberto Zaniboni

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.