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Various Advanced CancerPhase 1/2CheckMate358NCT02488759

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

A Phase 1/2 study testing Nivolumab, Ipilimumab and Relatlimab in people with Various Advanced Cancer, run by Bristol-Myers Squibb at 40 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Various Advanced Cancer
What is being tested?
Nivolumab, Ipilimumab and Relatlimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
578 participants
Where
40 sitesin 11 countries
Study dates
13 Oct 2015to 24 Oct 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathologic confirmation of the following tumor types (please refer to protocol for full details pertaining to eligible tumor types):
  • Merkel Cell Carcinoma
  • Gastric or Gastro-Esophageal junction carcinoma (No longer enrolling this tumor type)
  • Nasopharyngeal Carcinoma
  • Squamous cell carcinoma (SCC) of the cervix, vagina, or vulva
  • Squamous cell carcinoma of the Head and Neck
Show all 12Show fewer
  • Squamous cell carcinoma of the anal canal and penis
  • 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

Who cannot join

  • 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

Trial locations and contacts

40 sites in 11 countries.

40 sites in 11 countries

United States14 sites

  • Local Institution - 0035

    Ann Arbor, Michigan, 48109

  • Local Institution - 0003

    Atlanta, Georgia, 30322

  • Local Institution - 0002

    Boston, Massachusetts, 02114

  • Local Institution - 0019

    Boston, Massachusetts, 02114

  • Local Institution - 0020

    Boston, Massachusetts, 02114

  • Local Institution - 0022

    Charlotte, North Carolina, 28204

  • Local Institution - 0023

    Lutherville, Maryland, 21093

  • Local Institution - 0036

    New York, New York, 10065

  • Local Institution - 0005

    Oklahoma City, Oklahoma, 73104

  • Local Institution - 0029

    Pittsburgh, Pennsylvania, 15232

  • Local Institution - 0004

    Portland, Oregon, 97213

  • Local Institution - 0021

    Seattle, Washington, 98109

  • Local Institution - 0001

    Sioux Falls, South Dakota, 57104

  • Local Institution - 0033

    Tampa, Florida, 33612-9497

Other trials in United States

France4 sites

  • Local Institution - 0031

    Marseille, 13273

  • Local Institution - 0038

    Paris, 75475

  • Local Institution - 0032

    Toulouse, 31059

  • Local Institution - 0030

    Vlllejuif, 94800

Other trials in France

Belgium3 sites

  • Local Institution - 0012

    Brussels, 1000

  • Local Institution - 0014

    Brussels, 1090

  • Local Institution - 0013

    Brussels, 1200

Other trials in Belgium

Japan3 sites

  • Local Institution - 0040

    Chuo-ku, Tokyo, 1040045

  • Local Institution - 0039

    Kashiwa-shi, Chiba, 2778577

  • Local Institution - 0041

    Koto-ku, Tokyo, 135-8550

Other trials in Japan

Mexico3 sites

  • Local Institution - 0046

    Mérida, Yucatán, 97138

  • Local Institution - 0056

    Mexico City, Mexico City, 04700

  • Local Institution

    Oaxaca City, Oaxaca, 68040

Other trials in Mexico

Spain3 sites

  • Local Institution - 0018

    Barcelona, 08035

  • Local Institution - 0017

    Madrid, 28050

  • Local Institution - 0016

    Navarra, 31008

Other trials in Spain

United Kingdom3 sites

  • Local Institution - 0010

    Birmingham, West Midlands, B15 2TH

  • Local Institution - 0006

    Glasgow, Lanarkshire, G12 OYN

  • Local Institution - 0008

    London, W1T 7HA

Other trials in United Kingdom

Germany2 sites

  • Local Institution - 0027

    Essen, 45147

  • Local Institution - 0028

    Heilbronn, 74078

Other trials in Germany

Netherlands2 sites

  • Local Institution - 0011

    Amsterdam, 1066 CX

  • Local Institution - 0034

    Utrecht, 3584CX

Other trials in Netherlands

Taiwan2 sites

  • Local Institution - 0037

    Tainan, 70403

  • Local Institution - 0026

    Taipei, 10002

Other trials in Taiwan

South Korea1 site

  • Local Institution - 0024

    Seoul, 03080

Other trials in South Korea

About this study

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

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
Being tested
Nivolumab, Ipilimumab, Relatlimab, Daratumumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02488759
Study groupRoleWhat they receive
Neoadjuvant CohortExperimentalNivolumab intravenous infusion as specified **Not participating: Japan, Korea, and Taiwan
Receives: Drug: Nivolumab
Metastatic Monotherapy CohortExperimentalNivolumab intravenous infusion as specified
Receives: Drug: Nivolumab
Nivolumab plus Ipilimumab CohortExperimentalNivolumab 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
Receives: Drug: Nivolumab; Drug: Ipilimumab
Nivolumab plus Relatlimab CohortExperimentalNivolumab 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
Receives: Drug: Nivolumab; Drug: Relatlimab
Nivolumab plus Daratumumab CohortExperimentalNivolumab 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
Receives: Drug: Nivolumab; Drug: Daratumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs)

    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

    Measured: From first dose to 30 days post last dose (Up to 2 months)

  2. Neoadjuvant: Number of Participants With Drug-Related Serious Adverse Events (SAEs)

    Number of participants with any grade of drug-related serious adverse events (SAEs) in Neoadjuvant cohort

    Measured: From first dose to 30 days post last dose (Up to 2 months)

  3. Neoadjuvant: Rate of Surgery Delay

    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.

    Participants with the following diseases will be assessed:

    1. HPV positive squamous cell carcinoma of the Head and Neck (SCCHN);
    2. HPV negative SCCHN;
    3. Cervical Carcinoma;
    4. Vaginal/Vulvar Carcinoma;
    5. Merkel Cell Carcinoma

    Measured: Day 29

  4. Metastatic: Investigator-Assessed Objective Response Rate (ORR)

    Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) 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)

    Measured: From the date of first dose to the date of the initial objectively documented tumor progression or the date of the last tumor assessment prior to subsequent therapy (Up to 65 months)

Secondary outcomes (3)

  1. Metastatic: Investigator-Assessed Duration of Response (DoR)

    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) NOTE: "Cervical, Randomized" and "Cervical, Pooled" are not mutually exclusive categories.

    Measured: From first confirmed response (complete response or partial response) to the date of the initial objectively documented tumor progression or death due to any cause, whichever occurs first (Up to 83 months)

  2. Metastatic: Overall Survival (OS)

    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) Note: "Cervical, Randomized" and "Cervical, Pooled" are not mutually exclusive categories

    Measured: From the first dosing date to the date of death (Up to 83 months)

  3. Metastatic: Investigator-Assessed Progression-Free Survival (PFS)

    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 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) Note: "Cervical, Randomized" and "Cervical, Pooled" are not mutually exclusive categories

    Measured: From the first dosing date to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 83 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2015 (estimated)
  2. Study start13 Oct 2015
  3. Primary completion19 Mar 2021
  4. Study completion24 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
578 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02488759
Sponsor's protocol ID
CA209-358
Other IDs
2015-000230-29, 2015
Acronym
CheckMate358
Status last verified
Nov 2023
First submitted
30 Jun 2015
Last updated
13 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bhatia S, Topalian SL, Sharfman W, Meyer T, Steven N, Lao CD, Farinas-Madrid L, Devriese LA, Moore K, Ferris RL, Honma Y, Elias I, Srirangam A, Garnett-Benson C, Lee M, Nghiem P. Nivolumab With or Without Ipilimumab in Patients With Recurrent or Metastatic Merkel Cell Carcinoma: A Nonrandomized, Open-Label, International, Multicenter Phase I/II Study. J Clin Oncol. 2025 Mar 20;43(9):1137-1147. doi: 10.1200/JCO-24-02138. Epub 2025 Jan 31.

    PubMed 39889250

  • Oaknin A, Moore K, Meyer T, Lopez-Picazo Gonzalez J, Devriese LA, Amin A, Lao CD, Boni V, Sharfman WH, Park JC, Tahara M, Topalian SL, Magallanes M, Molina Alavez A, Khan TA, Copigneaux C, Lee M, Garnett-Benson C, Wang X, Naumann RW. Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial. Lancet Oncol. 2024 May;25(5):588-602. doi: 10.1016/S1470-2045(24)00088-3. Epub 2024 Apr 9.

    PubMed 38608691

  • Pulliam T, Jani S, Jing L, Ryu H, Jojic A, Shasha C, Zhang J, Kulikauskas R, Church C, Garnett-Benson C, Gooley T, Chapuis A, Paulson K, Smith KN, Pardoll DM, Newell EW, Koelle DM, Topalian SL, Nghiem P. Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma. Cell Rep Med. 2024 Feb 20;5(2):101412. doi: 10.1016/j.xcrm.2024.101412. Epub 2024 Feb 10.

    PubMed 38340723

  • Ferris RL, Spanos WC, Leidner R, Goncalves A, Martens UM, Kyi C, Sharfman W, Chung CH, Devriese LA, Gauthier H, Chiosea SI, Vujanovic L, Taube JM, Stein JE, Li J, Li B, Chen T, Barrows A, Topalian SL. Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial. J Immunother Cancer. 2021 Jun;9(6):e002568. doi: 10.1136/jitc-2021-002568.

    PubMed 34083421

  • Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbe C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P. Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial. J Clin Oncol. 2020 Aug 1;38(22):2476-2487. doi: 10.1200/JCO.20.00201. Epub 2020 Apr 23.

    PubMed 32324435

  • Naumann RW, Hollebecque A, Meyer T, Devlin MJ, Oaknin A, Kerger J, Lopez-Picazo JM, Machiels JP, Delord JP, Evans TRJ, Boni V, Calvo E, Topalian SL, Chen T, Soumaoro I, Li B, Gu J, Zwirtes R, Moore KN. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. J Clin Oncol. 2019 Nov 1;37(31):2825-2834. doi: 10.1200/JCO.19.00739. Epub 2019 Sep 5.

    PubMed 31487218

  • Appelbaum J, Wells D, Hiatt JB, Steinbach G, Stewart FM, Thomas H, Nghiem P, Kapur RP, Thompson JA, Bhatia S. Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report. J Immunother Cancer. 2018 Aug 31;6(1):82. doi: 10.1186/s40425-018-0396-9.

    PubMed 30170630

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab, Ipilimumab and Relatlimab in people with Various Advanced Cancer, run by Bristol-Myers Squibb at 40 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, France, Belgium, Japan, Mexico and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02488759, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2023.

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