Various Advanced Cancer
Conditions
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
Interventions
DRUGNivolumab
DRUGIpilimumab
DRUGRelatlimab
DRUGDaratumumab
Sponsors
Ono Pharmaceutical Co. Ltd
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Countries
Belgium, France, Germany, Japan, Mexico, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
578 participants treated
Participants by arm
| Arm | Count |
|---|---|
| Metastatic Monotherapy Nivolumab IV over 30 minutes at 240 mg every 2 weeks for a maximum of 24 months or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever comes first | 113 |
| Metastatic Combo A Nivolumab 3 mg/kg IV over 30 minutes every 2 weeks + Ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks for a maximum of 24 months or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever comes first | 195 |
| Metastatic Combo B Nivolumab 1 mg/kg IV over 30 minutes + Ipilimumab 3 mg/kg IV over 30 minutes every 3 weeks for 4 doses followed by Nivolumab 240 mg IV over 30 minutes every 2 weeks for a maximum of 24 months or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever comes first | 133 |
| Metastatic Combo C Nivolumab 240 mg IV over 30 minutes + BMS-986016 (Relatlimab) 80 mg IV over 60 minutes administered every 2 weeks for a maximum of 24 months, or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever comes first | 8 |
| Metastatic Combo D Daratumumab 16 mg/kg IV weekly for the first 8 weeks. Starting at Week 3, Nivolumab 240 mg IV over 30 minutes every 2 weeks. Daratumumab 16 mg/kg every 2 weeks from Weeks 9-24. Starting at Week 25, Nivolumab 480 mg IV flat dose over 30 minutes every 4 weeks; daratumumab 16 mg/kg every 4 weeks for a maximum of 24 months or until progression, unacceptable toxicity, or withdrawal of consent, whichever comes first | 6 |
| Neoadjuvant Nivolumab administered intravenously (IV) over 30 minutes at 240 mg for 2 doses, on Day 1 and Day 15 | 123 |
| Total | 578 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 9 | 11 | 7 | 0 | 1 | 0 |
| Overall Study | Disease progression | 73 | 111 | 62 | 7 | 4 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Maximum clinical benefit | 3 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other reasons | 7 | 32 | 23 | 1 | 1 | 1 |
| Overall Study | Participant request to discontinue study treatment | 6 | 8 | 4 | 0 | 0 | 0 |
| Overall Study | Study drug toxicity | 11 | 33 | 31 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 0 | 3 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Metastatic Monotherapy | Total | Neoadjuvant | Metastatic Combo D | Metastatic Combo C | Metastatic Combo B | Metastatic Combo A |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.4 Years STANDARD_DEVIATION 13.5 | 56.4 Years STANDARD_DEVIATION 13.8 | 62.0 Years STANDARD_DEVIATION 12.7 | 66.5 Years STANDARD_DEVIATION 15.3 | 59.0 Years STANDARD_DEVIATION 7.6 | 48.2 Years STANDARD_DEVIATION 12.3 | 57.5 Years STANDARD_DEVIATION 13.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 6 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 56 Participants | 1 Participants | 0 Participants | 0 Participants | 10 Participants | 31 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 17 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 24 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) White | 86 Participants | 475 Participants | 113 Participants | 6 Participants | 8 Participants | 115 Participants | 147 Participants |
| Sex: Female, Male Female | 39 Participants | 316 Participants | 59 Participants | 3 Participants | 1 Participants | 129 Participants | 85 Participants |
| Sex: Female, Male Male | 74 Participants | 262 Participants | 64 Participants | 3 Participants | 7 Participants | 4 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 82 / 113 | 133 / 195 | 86 / 133 | 7 / 8 | 5 / 6 | 40 / 123 |
| other Total, other adverse events | 110 / 113 | 189 / 195 | 129 / 133 | 7 / 8 | 5 / 6 | 108 / 123 |
| serious Total, serious adverse events | 59 / 113 | 130 / 195 | 99 / 133 | 5 / 8 | 5 / 6 | 40 / 123 |
Outcome results
Primary
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)
Time frame: 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)
Population: All treated participants in the metastatic cohorts
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | MCC | 64.0 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Cervical | 26.3 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | EBV positive related gastric cancer | 14.3 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Vaginal/Vulvar | 20.0 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | HPV positive SCCHN | 11.5 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | NPC | 16.7 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | NPC | 26.2 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | HPV positive SCCHN | 31.0 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Other anogenital HPV associated cancers | 34.8 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Cervical | 31.1 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | MCC | 58.1 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Cervical second line | 39.1 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Cervical | 40.0 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Other anogenital HPV associated cancers | 28.6 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | Cervical first line | 36.4 Percentage of participants |
| Metastatic Combo C | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | HPV positive SCCHN | 0 Percentage of participants |
| Metastatic Combo D | Metastatic: Investigator-Assessed Objective Response Rate (ORR) | SCCHN I-O naive | 16.7 Percentage of participants |
Primary
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
Time frame: From first dose to 30 days post last dose (Up to 2 months)
Population: All treated participants in the neoadjuvant cohort
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Pulmonary AEs | 0 Participants |
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Endocrine AEs | 3 Participants |
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs | 4 Participants |
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Hepatic AEs | 3 Participants |
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Renal AEs | 0 Participants |
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Skin AEs | 9 Participants |
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction AEs | 5 Participants |
Primary
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
Time frame: From first dose to 30 days post last dose (Up to 2 months)
Population: All treated participants in the neoadjuvant cohort
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant | Neoadjuvant: Number of Participants With Drug-Related Serious Adverse Events (SAEs) | 6 Participants |
Primary
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
Time frame: Day 29
Population: All tumor reduction evaluable participants in the neoadjuvant cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neoadjuvant | Neoadjuvant: Rate of Surgery Delay | HPV positive SCCHN | 0 Percentage of participants |
| Neoadjuvant | Neoadjuvant: Rate of Surgery Delay | HPV negative SCCHN | 0 Percentage of participants |
| Neoadjuvant | Neoadjuvant: Rate of Surgery Delay | Cervical Carcinoma | 7.7 Percentage of participants |
| Neoadjuvant | Neoadjuvant: Rate of Surgery Delay | Vaginal/Vulvar Carcinoma | 0 Percentage of participants |
| Neoadjuvant | Neoadjuvant: Rate of Surgery Delay | Merkel Cell Carcinoma | 2.7 Percentage of participants |
Secondary
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.
Time frame: 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)
Population: All complete and partial responders in the metastatic cohorts
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Neoadjuvant | Metastatic: Investigator-Assessed Duration of Response (DoR) | Cervical, Randomized | NA Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Duration of Response (DoR) | HPV positive SCCHN | 44.25 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Duration of Response (DoR) | MCC | 60.62 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Duration of Response (DoR) | Vaginal/Vulvar | 4.96 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Duration of Response (DoR) | EBV positive related gastric cancer | NA Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Duration of Response (DoR) | NPC | 9.46 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Duration of Response (DoR) | NPC | 19.63 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Duration of Response (DoR) | HPV positive SCCHN | 34.46 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Duration of Response (DoR) | Other anogenital HPV associated cancers | 18.23 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Duration of Response (DoR) | Cervical, Randomized | NA Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Duration of Response (DoR) | MCC | 25.86 Months |
| Metastatic Combo B | Metastatic: Investigator-Assessed Duration of Response (DoR) | Cervical, Randomized | 34.07 Months |
| Metastatic Combo B | Metastatic: Investigator-Assessed Duration of Response (DoR) | Other anogenital HPV associated cancers | 3.71 Months |
| Metastatic Combo B | Metastatic: Investigator-Assessed Duration of Response (DoR) | Cervical, Pooled | 34.07 Months |
| Metastatic Combo D | Metastatic: Investigator-Assessed Duration of Response (DoR) | SCCHN I-O naive | NA Months |
Secondary
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
Time frame: 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)
Population: All treated participants in the metastatic cohorts
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Neoadjuvant | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | MCC | 21.32 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Cervical, Randomized | 5.09 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | EBV positive related gastric cancer | 2.94 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Vaginal/Vulvar | 3.75 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | HPV positive SCCHN | 3.25 Months |
| Neoadjuvant | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | NPC | 1.94 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | NPC | 5.36 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | HPV positive SCCHN | 3.71 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Other anogenital HPV associated cancers | 4.63 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Cervical, Randomized | 3.75 Months |
| Metastatic Combo A | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | MCC | 8.39 Months |
| Metastatic Combo B | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Cervical, Randomized | 7.11 Months |
| Metastatic Combo B | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Other anogenital HPV associated cancers | 3.58 Months |
| Metastatic Combo B | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | Cervical, Pooled | 5.85 Months |
| Metastatic Combo C | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | HPV positive SCCHN | 3.81 Months |
| Metastatic Combo D | Metastatic: Investigator-Assessed Progression-Free Survival (PFS) | SCCHN I-O naive | 1.81 Months |
Secondary
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
Time frame: From the first dosing date to the date of death (Up to 83 months)
Population: All treated participants in the metastatic cohorts
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Neoadjuvant | Metastatic: Overall Survival (OS) | MCC | 80.66 Months |
| Neoadjuvant | Metastatic: Overall Survival (OS) | Cervical, Randomized | 21.55 Months |
| Neoadjuvant | Metastatic: Overall Survival (OS) | EBV positive related gastric cancer | 9.99 Months |
| Neoadjuvant | Metastatic: Overall Survival (OS) | Vaginal/Vulvar | 10.28 Months |
| Neoadjuvant | Metastatic: Overall Survival (OS) | HPV positive SCCHN | 20.44 Months |
| Neoadjuvant | Metastatic: Overall Survival (OS) | NPC | 22.74 Months |
| Metastatic Combo A | Metastatic: Overall Survival (OS) | NPC | 23.66 Months |
| Metastatic Combo A | Metastatic: Overall Survival (OS) | HPV positive SCCHN | 17.08 Months |
| Metastatic Combo A | Metastatic: Overall Survival (OS) | Other anogenital HPV associated cancers | 12.12 Months |
| Metastatic Combo A | Metastatic: Overall Survival (OS) | Cervical, Randomized | 17.12 Months |
| Metastatic Combo A | Metastatic: Overall Survival (OS) | MCC | 29.83 Months |
| Metastatic Combo B | Metastatic: Overall Survival (OS) | Cervical, Randomized | 22.74 Months |
| Metastatic Combo B | Metastatic: Overall Survival (OS) | Other anogenital HPV associated cancers | 14.06 Months |
| Metastatic Combo B | Metastatic: Overall Survival (OS) | Cervical, Pooled | 20.93 Months |
| Metastatic Combo C | Metastatic: Overall Survival (OS) | HPV positive SCCHN | 8.84 Months |
| Metastatic Combo D | Metastatic: Overall Survival (OS) | SCCHN I-O naive | 4.21 Months |
Post Hoc
Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection
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) Note: Cervical, Randomized and Cervical, Pooled are not mutually exclusive categories
Time frame: 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 83 months)
Population: All treated participants in the metastatic cohorts
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | MCC | 60.0 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Cervical, Randomized | 26.3 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | EBV positive related gastric cancer | 14.3 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Vaginal/Vulvar | 20.0 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | HPV positive SCCHN | 11.5 Percentage of participants |
| Neoadjuvant | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | NPC | 16.7 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | NPC | 28.6 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | HPV positive SCCHN | 31.0 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Other anogenital HPV associated cancers | 34.8 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Cervical, Randomized | 31.1 Percentage of participants |
| Metastatic Combo A | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | MCC | 58.1 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Cervical, Randomized | 40.0 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Other anogenital HPV associated cancers | 23.8 Percentage of participants |
| Metastatic Combo B | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | Cervical, Pooled | 40.2 Percentage of participants |
| Metastatic Combo C | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | HPV positive SCCHN | 0 Percentage of participants |
| Metastatic Combo D | Metastatic: Investigator-Assessed Objective Response Rate (ORR) Extended Collection | SCCHN I-O naive | 16.7 Percentage of participants |