Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Clinical Trials

Abstract CT101: A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types

Xiaochen Zhao, Vijay Ivaturi, Mathangi Gopalakrishnan, Jun Shen, Yan Feng, Paul Statkevich, Eric Richards, Michelle Rashford, Vicki Goodman, Joga Gobburu, Akintunde Bello, Amit Roy and Shruti Agrawal
Xiaochen Zhao
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vijay Ivaturi
Global Pharmaceutical Advisors, Baltimore, MD.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mathangi Gopalakrishnan
Global Pharmaceutical Advisors, Baltimore, MD.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun Shen
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yan Feng
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Statkevich
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Richards
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelle Rashford
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vicki Goodman
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joga Gobburu
Global Pharmaceutical Advisors, Baltimore, MD.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akintunde Bello
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amit Roy
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shruti Agrawal
Bristol-Myers Squibb, Princeton, NJ;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2017-CT101 Published July 2017
  • Article
  • Info & Metrics
Loading
Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC

Abstract

Introduction: The anti-PD-1 checkpoint inhibitor NIVO provides favorable safety and efficacy when administered at 3 mg/kg Q2W across multiple tumor types. Alternative dosing schedules would provide flexibility and offer benefits to patients and prescribers. A well-established understanding of NIVO clinical pharmacology, robust clinical data across multiple tumor types and well characterized, relatively flat E-R relationships for efficacy and safety support the use of model-based approaches to qualify other potential NIVO doses and schedules.

Methods: The feasibility of extending the dosing interval of NIVO from Q2W to Q4W was investigated using a combination of quantitative clinical pharmacology analyses and safety assessments. The predicted benefit-risk profile of NIVO 480 mg Q4W relative to 3 mg/kg Q2W was assessed by the following analyses: (1) comparison of NIVO exposures produced by 3 mg/kg Q2W and 480 mg Q4W across tumor types; (2) evaluation of NIVO exposure margins for safety relative to the well-tolerated dose of 10 mg/kg Q2W; (3) comparison of predicted risk of experiencing adverse events (Gr3+ AEs, immune-mediated AEs) with 480 mg Q4W relative to 3 mg/kg Q2W across indications of melanoma, NSCLC, RCC, UC, H&N and cHL; and (4) comparison of predicted objective tumor response (OR) and overall survival with NIVO 480 mg Q4W relative to 3 mg/kg Q2W in patients with melanoma, NSCLC, and RCC.

Results: Steady-state peak, time-averaged, and trough NIVO concentrations predicted with 480 mg Q4W were approximately 44% higher, 4% higher, and 18% lower, respectively, compared with 3 mg/kg Q2W. The aggregate of safety data accumulated for NIVO up to a dose level of 10 mg/kg Q2W in multiple tumor types provides a wide safety margin for the maximum concentration values expected with 480 mg Q4W. The steady-state exposures produced by 480 mg Q4W were lower than the corresponding exposures with 10 mg/kg Q2W, which has been shown to have acceptable safety and tolerability. The predicted probabilities of achieving an OR with NIVO 480 mg Q4W were similar to those with 3 mg/kg Q2W (<1% difference) across tumor types. Predicted 1- and 2-year survival probabilities were also similar to that of NIVO 3 mg/kg Q2W (differences ranging between 0%-4.6% at year 1, and 1.9%-6.9% at year 2) across tumor types.

Conclusion: With a well-established understanding of NIVO clinical pharmacology, robust clinical data across multiple tumor types and well-characterized E-R relationships for efficacy and safety, the differences in exposures produced by a NIVO schedule of 480 mg Q4W relative to 3 mg/kg Q2W dosing schedule are not expected to result in clinically meaningful differences in the safety and efficacy of NIVO. The proposed 480 mg Q4W schedule has been incorporated into NIVO clinical trials (NCT02713867, NCT02714218) across multiple tumor types.

Citation Format: Xiaochen Zhao, Vijay Ivaturi, Mathangi Gopalakrishnan, Jun Shen, Yan Feng, Paul Statkevich, Eric Richards, Michelle Rashford, Vicki Goodman, Joga Gobburu, Akintunde Bello, Amit Roy, Shruti Agrawal. A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT101. doi:10.1158/1538-7445.AM2017-CT101

  • ©2017 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 77 (13 Supplement)
July 2017
Volume 77, Issue 13 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract CT101: A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract CT101: A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types
Xiaochen Zhao, Vijay Ivaturi, Mathangi Gopalakrishnan, Jun Shen, Yan Feng, Paul Statkevich, Eric Richards, Michelle Rashford, Vicki Goodman, Joga Gobburu, Akintunde Bello, Amit Roy and Shruti Agrawal
Cancer Res July 1 2017 (77) (13 Supplement) CT101; DOI: 10.1158/1538-7445.AM2017-CT101

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract CT101: A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types
Xiaochen Zhao, Vijay Ivaturi, Mathangi Gopalakrishnan, Jun Shen, Yan Feng, Paul Statkevich, Eric Richards, Michelle Rashford, Vicki Goodman, Joga Gobburu, Akintunde Bello, Amit Roy and Shruti Agrawal
Cancer Res July 1 2017 (77) (13 Supplement) CT101; DOI: 10.1158/1538-7445.AM2017-CT101
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Clinical Trials

  • Abstract CT130: PANOVA: A phase II study of TTFields (150kHz) concomitant with standard chemotherapy for front line therapy of advanced pancreatic adenocarcinoma
  • Abstract CT076: Multicenter phase II study of nivolumab in previously treated patients with recurrent and metastatic non-keratinizing nasopharyngeal carcinoma - Mayo clinic Phase 2 Consortium P2C-MN026, NCI9742, NCT02339558
  • Abstract CT033: Phase I study of intraventricular infusions of autologous exvivo expanded NK cells in children with recurrent/refractory malignant posterior fossa tumors of the central nervous system
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract LB-236: Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013
  • Abstract LB-001: Impact of direct physician engagement with racial/ethnic minorities for oncology clinical trial access and accrual model
  • Abstract LB-107: EV-TRACK: transparent reporting and centralizing knowledge of extracellular vesicles to support the validation of extracellular vesicle biomarkers in cancer research
Show more 3

Poster Presentations - Phase I Clinical Trials

  • Abstract CT098: Phase 1 first-in-human study of anti-clusterin antibody AB-16B5 in patients with advanced solid malignancies
  • Abstract CT105: Validation of a tobacco smoke exposure gene expression signature and exploration of intraoral metabolite profiles following administration of a strawberry functional confection in smokers and nonsmokers
  • Abstract CT085: iCare 1: A prospective clinical trial to predict treatment response based on mutanome-informed computational biology in patients with AML and MDS
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement