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An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors (CheckMate358)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02488759
Recruitment Status : Active, not recruiting
First Posted : July 2, 2015
Results First Posted : April 12, 2022
Last Update Posted : July 7, 2022
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:

The purpose of this study to investigate the safety and effectiveness of nivolumab, and nivolumab combination therapy, to treat patients who have virus-associated tumors. Certain viruses have been known to play a role in tumor formation and growth. This study will investigate the effects of the study drugs, in patients who have the following types of tumors:

  • Anal canal cancer-No longer enrolling this tumor type
  • Cervical cancer
  • Epstein Barr Virus (EBV) positive gastric cancer-No longer enrolling this tumor type
  • Merkel Cell Cancer
  • Penile cancer-No longer enrolling this tumor type
  • Vaginal and vulvar cancer-No longer enrolling this tumor type
  • Nasopharyngeal Cancer - No longer enrolling this tumor type
  • Head and Neck Cancer - No longer enrolling this tumor type

Condition or disease Intervention/treatment Phase
Various Advanced Cancer Drug: Nivolumab Drug: Ipilimumab Drug: Relatlimab Drug: Daratumumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 578 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-Comparative, Open-Label, Multiple Cohort, Phase 1/2 Study of Nivolumab Monotherapy and Nivolumab Combination Therapy in Subjects With Virus-Positive and Virus-Negative Solid Tumors
Actual Study Start Date : October 13, 2015
Actual Primary Completion Date : March 19, 2021
Estimated Study Completion Date : August 4, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Viral Infections

Arm Intervention/treatment
Experimental: Neoadjuvant Cohort

Nivolumab intravenous infusion as specified

**Not participating: Japan, Korea, and Taiwan

Drug: Nivolumab
Experimental: Metastatic Monotherapy Cohort
Nivolumab intravenous infusion as specified
Drug: Nivolumab
Experimental: Nivolumab plus Ipilimumab Cohort

Nivolumab intravenous infusion as specified with Ipilimumab intravenous infusion as specified

**Not participating: Belgium, France and Germany

Cohort expansion participating countries: Spain, US, UK, Netherlands, Japan and Mexico

**Not participating in cohort expansion: France, Germany, Korea and Taiwan

Drug: Nivolumab
Drug: Ipilimumab
Experimental: Nivolumab plus Relatlimab Cohort

Nivolumab intravenous infusion as specified with Relatlimab intravenous infusion as specified

** Not Participating: Belgium, Germany, France, Japan, Korea, Taiwan, UK, and Netherlands

Enrollment is closed for this cohort

Drug: Nivolumab
Drug: Relatlimab
Other Names:
  • BMS-986016
  • Anti-LAG 3

Experimental: Nivolumab plus Daratumumab Cohort

Nivolumab intravenous infusion as specified with Daratumumab intravenous infusion as specified

**Not Participating: Belgium, Germany, France, Japan, Korea, Taiwan, UK, and Netherlands

Enrollment is closed for this cohort

Drug: Nivolumab
Drug: Daratumumab
Other Name: Darzalex




Primary Outcome Measures :
  1. Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) [ Time Frame: From first dose to 30 days post last dose (Up to 2 months) ]
    Number of participants with any grade of drug-related select adverse events (AEs) including endocrine, gastrointestinal, hepatic, pulmonary, renal, skin, and hypersensitivity AEs in Neoadjuvant cohort

  2. Neoadjuvant: Number of Participants With Drug-Related Serious Adverse Events (SAEs) [ Time Frame: From first dose to 30 days post last dose (Up to 2 months) ]
    Number of participants with any grade of drug-related serious adverse events (SAEs) in Neoadjuvant cohort

  3. Neoadjuvant: Rate of Surgery Delay [ Time Frame: Day 29 ]
    Rate of surgery delay is defined as the percentage of participants in the neoadjuvant cohort with surgery delayed > 4 weeks from the planned surgery date or planned start date for chemoradiation due to a drug-related adverse event

  4. Metastatic: Investigator-Assessed Objective Response Rate (ORR) [ Time Frame: Up to 72 months ]

    Objective response rate (ORR) is defined as the the number of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) divided by the number of treated participants using RECIST 1.1 criteria. An ORR in excess of 10% will be considered of clinical interest, and an ORR of 25% or greater will be considered of strong clinical interest.

    Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Participants with the following diseases will be assessed:

    1. EBV positive related gastric cancer;
    2. HPV positive SCCHN;
    3. Other anogenital HPV associated cancers;
    4. GYN (Cervical, Vaginal, Vulvar) carcinoma;
    5. Merkel cell carcinoma (MCC);
    6. Nasopharyngeal carcinoma (NPC)


Secondary Outcome Measures :
  1. Metastatic: Investigator-Assessed Duration of Response (DoR) [ Time Frame: Up to 72 months ]

    Duration of response (DoR) is defined as the time from first confirmed response (complete response or partial response) to the date of the initial objectively documented tumor progression as determined per investigator assessment using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants with the following diseases will be assessed:

    1. EBV positive related gastric cancer;
    2. HPV positive SCCHN;
    3. Other anogenital HPV associated cancers;
    4. GYN (Cervical, Vaginal, Vulvar) carcinoma;
    5. Merkel cell carcinoma (MCC);
    6. Nasopharyngeal carcinoma (NPC)

  2. Metastatic: Overall Survival (OS) [ Time Frame: Up to 72 months ]

    Overall survival (OS) is defined as the time from first dosing date to the date of death. A participant who has not died will be censored at last known date alive. Participants with the following diseases will be assessed:

    1. EBV positive related gastric cancer;
    2. HPV positive SCCHN;
    3. Other anogenital HPV associated cancers;
    4. GYN (Cervical, Vaginal, Vulvar) carcinoma;
    5. Merkel cell carcinoma (MCC);
    6. Nasopharyngeal carcinoma (NPC)

  3. Metastatic: Investigator-Assessed Progression-Free Survival (PFS) [ Time Frame: Up to 72 months ]

    Investigator-assessed progression free survival (PFS) is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by investigators (per RECIST 1.1), or death due to any. Participants with the following diseases will be assessed:

    1. EBV positive related gastric cancer;
    2. HPV positive SCCHN;
    3. Other anogenital HPV associated cancers;
    4. GYN (Cervical, Vaginal, Vulvar) carcinoma;
    5. Merkel cell carcinoma (MCC);
    6. Nasopharyngeal carcinoma (NPC)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histopathologic confirmation of the following tumor types (please refer to protocol for full details pertaining to eligible tumor types):

    1. Merkel Cell Carcinoma
    2. Gastric or Gastro-Esophageal junction carcinoma (No longer enrolling this tumor type)
    3. Nasopharyngeal Carcinoma
    4. Squamous cell carcinoma (SCC) of the cervix, vagina, or vulva
    5. Squamous cell carcinoma of the Head and Neck
    6. Squamous cell carcinoma of the anal canal and penis
    7. Recurrent/metastatic SCC of the cervix not amenable to curative treatment with surgery and/or radiation therapy who are unsuitable for platinum-based therapy may enroll in the cervical cancer Combination B expansion cohort
  • Measurable disease by CT or MRI
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patient willing to comply to provide tumor tissue (archival or fresh biopsy specimen)
  • Men and women of age 18 or older

Exclusion Criteria:

  • Active brain metastases or leptomeningeal metastases
  • Patients with active, known or suspected autoimmune disease
  • Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
  • Patients with hepatitis
  • Patients with HIV
  • Pregnant or breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02488759


Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] May 7, 2019
Statistical Analysis Plan  [PDF] September 7, 2021

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02488759    
Other Study ID Numbers: CA209-358
2015-000230-29 ( EudraCT Number )
First Posted: July 2, 2015    Key Record Dates
Results First Posted: April 12, 2022
Last Update Posted: July 7, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Nivolumab
Ipilimumab
Daratumumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action