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

NCT02488759 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA209-3582015-000230-29
• Study Type: interventional
• Target: 578
• Locations: 11 countries
• Sites: 40

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

Conditions

Various Advanced Cancer

Outcome Measures

Primary Outcomes (4)

• 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

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

• 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

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

• 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

  Day 29

• 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)

  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)

• Metastatic: Investigator-Assessed Duration of Response (DoR)

  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)

• Metastatic: Overall Survival (OS)

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

• Metastatic: Investigator-Assessed Progression-Free Survival (PFS)

  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)

Study Arms (5)

Neoadjuvant Cohort

EXPERIMENTAL

Nivolumab intravenous infusion as specified \*\*Not participating: Japan, Korea, and Taiwan

Drug: Nivolumab

Metastatic Monotherapy Cohort

EXPERIMENTAL

Nivolumab intravenous infusion as specified

Drug: Nivolumab

Nivolumab plus Ipilimumab Cohort

EXPERIMENTAL

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

Nivolumab plus Relatlimab Cohort

EXPERIMENTAL

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

Nivolumab plus Daratumumab Cohort

EXPERIMENTAL

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

Interventions

Nivolumab DRUG

Metastatic Monotherapy Cohort; Neoadjuvant Cohort; Nivolumab plus Daratumumab Cohort; Nivolumab plus Ipilimumab Cohort; Nivolumab plus Relatlimab Cohort

Ipilimumab DRUG

Nivolumab plus Ipilimumab Cohort

Relatlimab DRUG

Also known as: BMS-986016, Anti-LAG 3

Nivolumab plus Relatlimab Cohort

Daratumumab DRUG

Also known as: Darzalex

Nivolumab plus Daratumumab Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (40)

Local Institution - 0033

Tampa, Florida, 33612-9497, United States

Location

Local Institution - 0003

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0023

Lutherville, Maryland, 21093, United States

Location

Local Institution - 0002

Boston, Massachusetts, 02114, United States

Location

Local Institution - 0019

Boston, Massachusetts, 02114, United States

Location

Local Institution - 0020

Boston, Massachusetts, 02114, United States

Location

Local Institution - 0035

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 0036

New York, New York, 10065, United States

Location

Local Institution - 0022

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0005

Oklahoma City, Oklahoma, 73104, United States

Location

Local Institution - 0004

Portland, Oregon, 97213, United States

Location

Local Institution - 0029

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 0001

Sioux Falls, South Dakota, 57104, United States

Location

Local Institution - 0021

Seattle, Washington, 98109, United States

Location

Local Institution - 0012

Brussels, 1000, Belgium

Location

Local Institution - 0014

Brussels, 1090, Belgium

Location

Local Institution - 0013

Brussels, 1200, Belgium

Location

Local Institution - 0031

Marseille, 13273, France

Location

Local Institution - 0038

Paris, 75475, France

Location

Local Institution - 0032

Toulouse, 31059, France

Location

Local Institution - 0030

Vlllejuif, 94800, France

Location

Local Institution - 0027

Essen, 45147, Germany

Location

Local Institution - 0028

Heilbronn, 74078, Germany

Location

Local Institution - 0039

Kashiwa-shi, Chiba, 2778577, Japan

Location

Local Institution - 0040

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0041

Koto-ku, Tokyo, 135-8550, Japan

Location

Local Institution - 0056

Mexico City, Mexico City, 04700, Mexico

Location

Local Institution

Oaxaca City, Oaxaca, 68040, Mexico

Location

Local Institution - 0046

Mérida, Yucatán, 97138, Mexico

Location

Local Institution - 0011

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0034

Utrecht, 3584CX, Netherlands

Location

Local Institution - 0024

Seoul, 03080, South Korea

Location

Local Institution - 0018

Barcelona, 08035, Spain

Location

Local Institution - 0017

Madrid, 28050, Spain

Location

Local Institution - 0016

Navarra, 31008, Spain

Location

Local Institution - 0037

Tainan, 70403, Taiwan

Location

Local Institution - 0026

Taipei, 10002, Taiwan

Location

Local Institution - 0006

Glasgow, Lanarkshire, G12 OYN, United Kingdom

Location

Local Institution - 0010

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Local Institution - 0008

London, W1T 7HA, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 39889250 DERIVED

• 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.

  PMID: 38608691 DERIVED

• 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.

  PMID: 38340723 DERIVED

• 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.

  PMID: 34083421 DERIVED

• 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.

  PMID: 32324435 DERIVED

• 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.

  PMID: 31487218 DERIVED

• 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.

  PMID: 30170630 DERIVED

Related Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form

MeSH Terms

Interventions

Nivolumab; Ipilimumab; relatlimab; daratumumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 2, 2015
• Study Start: October 13, 2015
• Primary Completion: March 19, 2021
• Study Completion: October 24, 2022
• Last Updated: November 13, 2023
• Results First Posted: April 12, 2022

Record last verified: 2023-11

Locations

JP (3); US (14); DE (2); TW (2); FR (4); BE (3); ME (3); NL (2); GB (3); ES (3); KR (1)