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

Phase 1

Completed

Conditions: Various Advanced Cancer

Interventions: Drug: Nivolumab
Drug: Ipilimumab
Drug: Daratumumab
Drug: Relatlimab

Registration Number: NCT02488759

Lead Sponsor: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 578

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neoadjuvant Cohort	Nivolumab	Nivolumab intravenous infusion as specified \\Not participating: Japan, Korea, and Taiwan
Metastatic Monotherapy Cohort	Nivolumab	Nivolumab intravenous infusion as specified
Nivolumab plus Ipilimumab Cohort	Nivolumab	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
Nivolumab plus Ipilimumab Cohort	Ipilimumab	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
Nivolumab plus Relatlimab Cohort	Nivolumab	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
Nivolumab plus Daratumumab Cohort	Nivolumab	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
Nivolumab plus Daratumumab Cohort	Daratumumab	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
Nivolumab plus Relatlimab Cohort	Relatlimab	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

Primary Outcome Measures

Name	Time	Method
Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs)	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
Neoadjuvant: Number of Participants With Drug-Related Serious Adverse Events (SAEs)	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
Neoadjuvant: Rate of Surgery Delay	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. 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
Metastatic: Investigator-Assessed Objective Response Rate (ORR)	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)	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)

Secondary Outcome Measures

Name	Time	Method
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)	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.
Metastatic: Overall Survival (OS)	From the first dosing date to the date of death (Up to 83 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) Note: "Cervical, Randomized" and "Cervical, Pooled" are not mutually exclusive categories
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)	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

Trial Locations

Locations (40): Local Institution - 0003
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Atlanta, Georgia, United States
Local Institution - 0012
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Brussels, Belgium
Local Institution - 0033
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Tampa, Florida, United States
Local Institution - 0020
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Boston, Massachusetts, United States
Local Institution - 0016
🇪🇸
Navarra, Spain
Local Institution - 0004
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Portland, Oregon, United States
Local Institution - 0037
🇨🇳
Tainan, Taiwan
Local Institution - 0021
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Seattle, Washington, United States
Local Institution - 0019
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Boston, Massachusetts, United States
Local Institution - 0041
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Koto-ku, Tokyo, Japan
Local Institution
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Oaxaca de Juarez, Oaxaca, Mexico
Local Institution - 0030
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Vlllejuif, France
Local Institution - 0032
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Toulouse Cedex 9, France
Local Institution - 0011
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Amsterdam, Netherlands
Local Institution - 0026
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Taipei, Taiwan
Local Institution - 0040
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Chuo-ku, Tokyo, Japan
Local Institution - 0034
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Utrecht, Netherlands
Local Institution - 0017
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Madrid, Spain
Local Institution - 0031
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Marseille Cedex 9, France
Local Institution - 0038
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Paris, France
Local Institution - 0014
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Brussels, Belgium
Local Institution - 0013
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Bruxelles, Belgium
Local Institution - 0027
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Essen, Germany
Local Institution - 0024
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Seoul, Korea, Republic of
Local Institution - 0018
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Barcelona, Spain
Local Institution - 0008
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London, United Kingdom
Local Institution - 0002
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Boston, Massachusetts, United States
Local Institution - 0023
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Lutherville, Maryland, United States
Local Institution - 0036
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New York, New York, United States
Local Institution - 0035
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Ann Arbor, Michigan, United States
Local Institution - 0029
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Pittsburgh, Pennsylvania, United States
Local Institution - 0022
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Charlotte, North Carolina, United States
Local Institution - 0028
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Heilbronn, Germany
Local Institution - 0039
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Kashiwa-shi, Chiba, Japan
Local Institution - 0056
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Mexico City, Distrito Federal, Mexico
Local Institution - 0046
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Merida, Yucatan, Mexico
Local Institution - 0006
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Glasgow, Lanarkshire, United Kingdom
Local Institution - 0010
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Birmingham, West Midlands, United Kingdom
Local Institution - 0001
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Sioux Falls, South Dakota, United States
Local Institution - 0005
🇺🇸
Oklahoma City, Oklahoma, United States

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