Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)

• ClinicalTrials.gov Identifier: NCT02105636
• Recruitment Status: Completed
• First Posted: April 7, 2014
• Results First Posted: January 11, 2017
• Last Update Posted: October 5, 2022
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: April 3, 2014
• First Posted Date: April 7, 2014
• Results First Submitted Date: November 15, 2016
• Results First Posted Date: January 11, 2017
• Last Update Posted Date: October 5, 2022
• Actual Study Start Date: May 29, 2014
• Actual Primary Completion Date: November 6, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 6, 2022)

Overall Survival (OS) [ Time Frame: From date of randomization to date of death (Up to approximately 18 months) ]

OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method.

Original Primary Outcome Measures (submitted: April 4, 2014)

• Progression-Free Survival (PFS) [ Time Frame: Approximately 26 months ]
  Starting at week 9 and then every 6 weeks after randomization, until disease progression
• Overall Survival (OS) [ Time Frame: Approximately 3.5 years ]
  Every 3 months during the survival follow-up phase

Current Secondary Outcome Measures (submitted: September 6, 2022)

• Investigator-Assessed Progression-Free Survival (PFS) [ Time Frame: From date of randomization to date of disease progression or death, whichever occurs first (Up to approximately 87 months) ]
  PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)), or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5mm. Participants who:

  • Die without a reported progression were considered to have progressed on the date of their death.
  • Did not progress or die were censored on the date of their last evaluable tumor assessment.
  • Without any on study tumor assessments and did not die were censored on their date of randomization.
  • Received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy.
• Investigator-Assessed Objective Response Rate (ORR) [ Time Frame: From date of randomization to date of disease progression or study drug is discontinued, whichever occurs first (Up to approximately 87 months) ]
  ORR was defined as the percentage of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

Original Secondary Outcome Measures (submitted: April 4, 2014)

Objective Response Rate [ Time Frame: Approximately 3.5 years ]

Starting at week 9 and then every 6 weeks after randomization, until disease progression or study drug is discontinued (whichever occurs later)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)
• Official Title: An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Brief Summary: The purpose of this study is to find out whether Nivolumab will significantly improve overall survival as compared to therapy of investigator's choice in patients with recurrent or metastatic head and neck carcinoma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Squamous Cell Carcinoma of the Head and Neck

Intervention

• Drug: Nivolumab
  Other Name: BMS-936558
• Drug: Cetuximab
• Drug: Methotrexate
• Drug: Docetaxel

Study Arms

• Experimental: Arm A: Nivolumab
  Nivolumab 3mg/kg intravenous (IV) Solution for Injection every 2 weeks until disease progression
  Intervention: Drug: Nivolumab
• Active Comparator: Arm B: Cetuximab/Methotrexate/Docetaxel

  Cetuximab intravenous (IV) Solution for Injection 400 mg/m2 (first dose) then 250 mg/m2 weekly until disease progression

  OR

  Methotrexate intravenous (IV) Solution for Injection 40 or 60 mg/m2 weekly until disease progression

  OR

  Docetaxel intravenous (IV) Solution for Injection 30 or 40 mg/m2 weekly until disease progression

  Interventions:

  • Drug: Cetuximab
  • Drug: Methotrexate
  • Drug: Docetaxel

Publications *

• Yen CJ, Kiyota N, Hanai N, Takahashi S, Yokota T, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH, Li WSK, Ferris RL, Gillison M, Endo T, Jayaprakash V, Tahara M. Two-year follow-up of a randomized phase III clinical trial of nivolumab vs. the investigator's choice of therapy in the Asian population for recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141). Head Neck. 2020 Oct;42(10):2852-2862. doi: 10.1002/hed.26331. Epub 2020 Jun 24.
• Saba NF, Blumenschein G Jr, Guigay J, Licitra L, Fayette J, Harrington KJ, Kiyota N, Gillison ML, Ferris RL, Jayaprakash V, Li L, Brossart P. Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age. Oral Oncol. 2019 Sep;96:7-14. doi: 10.1016/j.oraloncology.2019.06.017. Epub 2019 Jul 3.
• Cocks K, Contente M, Simpson S, DeRosa M, Taylor FC, Shaw JW. A Q-TWiST Analysis Comparing Nivolumab and Therapy of Investigator's Choice in Patients with Recurrent/Metastatic Platinum-Refractory Squamous Cell Carcinoma of the Head and Neck. Pharmacoeconomics. 2019 Aug;37(8):1041-1047. doi: 10.1007/s40273-019-00798-1.
• Pai SI, Faivre S, Licitra L, Machiels JP, Vermorken JB, Bruzzi P, Gruenwald V, Giglio RE, Leemans CR, Seiwert TY, Soulieres D. Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). J Immunother Cancer. 2019 Apr 3;7(1):96. doi: 10.1186/s40425-019-0578-0.
• Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Lynch M, Jayaprakash V, Li L, Gillison ML. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018 Jun;81:45-51. doi: 10.1016/j.oraloncology.2018.04.008. Epub 2018 Apr 17.
• Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen CJ, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH, Sum Kenneth Li W, Ferris RL, Gillison M, Namba Y, Monga M, Lynch M, Tahara M. A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol. 2017 Oct;73:138-146. doi: 10.1016/j.oraloncology.2017.07.023. Epub 2017 Sep 1.
• Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, Kasper S, Even C, Vokes EE, Worden F, Saba NF, Kiyota N, Haddad R, Tahara M, Grunwald V, Shaw JW, Monga M, Lynch M, Taylor F, DeRosa M, Morrissey L, Cocks K, Gillison ML, Guigay J. Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1104-1115. doi: 10.1016/S1470-2045(17)30421-7. Epub 2017 Jun 23.
• Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 6, 2022): 361
• Original Estimated Enrollment (submitted: April 4, 2014): 180
• Actual Study Completion Date: September 10, 2021
• Actual Primary Completion Date: November 6, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Men and women ≥ 18 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy)
• Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting
• Measurable disease by Computed tomography (CT) or Magnetic resonance imaging (MRI) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases are not allowed
• Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg: mucosal melanoma) are not allowed
• Subjects with active, known or suspected autoimmune disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02105636
• Other Study ID Numbers: CA209-141; 2013-003622-86 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Ono Pharmaceutical Co. Ltd

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: August 2022