Malignant Melanoma
Conditions
Brief summary
The purpose of this study is to determine the safety and tolerability of treatment with BMS-936558 (MDX-1106) in combination with Ipilimumab (BMS-734016) when given at the same time or as a sequenced regimen in subjects with unresectable Stage III or Stage IV malignant melanoma (MEL)
Interventions
DRUGBMS-936558 (MDX1106-04)
DRUGIpilimumab
Sponsors
Bristol-Myers Squibb
Medarex
Ono Pharma USA Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Histologic diagnosis of malignant melanoma (MEL) * Measurable unresectable Stage III or IV MEL * ECOG performance status score of 0 or 1 * Life expectancy ≥4 months * For those enrolled in amendment 5 and later, tumor tissue (archival or recent acquisition) must be available * For Cohorts 1-5, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma not including any post-incisional adjuvant therapy. Subjects may be treatment naïve. All metastatic melanoma regardless of primary site of disease will be allowed * For Cohorts 6-7, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma; this does not include any post-incisional adjuvant therapy. Specifically, subjects must have received ≥3 doses of Ipilimumab therapy and the last dose having been administered within 4-12 weeks of initiation of study treatment
Exclusion criteria
* History of severe hypersensitivity reactions to other mAbs * Prior malignancy active within the previous 2 years except for localized cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence * Active autoimmune disease or a history of known or suspected autoimmune disease * History of recently active diverticulitis or symptomatic peptic ulcer disease and history of adrenal insufficiency * Regular narcotic analgesia * Active, untreated central nervous system metastasis * For subjects enrolled in Cohorts 1-5, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody * For subjects enrolled in Cohorts 6-7, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD137 antibodies * Any non-oncology vaccine therapy used for prevention of infectious disease * Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs * Positive tests for human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), hepatitis B, hepatitis C * Subjects weighing ≥125 kg are excluded from Cohort 5 * Subjects in Cohorts 6 and 7 must have received Ipilimumab monotherapy immediately prior to study entry, but must not have received that Ipilimumab as part of a clinical trial * Subjects with ocular melanoma are excluded from Cohort 8
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Adverse Event (AE) | Up to 3 years | incidence of all cause and treatment related adverse events |
| Number of Participants With a Serious Adverse Event (AE) | Up to 3 years | incidence of all cause and treatment related serious adverse events |
| Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Up to 3 years | incidence of all cause and treatment related adverse events which lead to discontinuation |
| Number of Deaths | Up to 3 years | incidence of all cause and treatment related deaths |
| Number of Participants With Select AEs | Up to 3 years | incidence of all cause and treatment related Adverse events in certain organ systems |
| Laboratory Abnormalities: Specific Liver Tests | Up to 3 years | Number of Participants with On-Treatment Laboratory Abnormalities in Specific Liver Tests Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) |
| Laboratory Abnormalities: Specific Thyroid Tests | Up to 3 years | Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 3 years | the total number of participants whose best overall response (BOR) is either irCR or irPR divided by the total number of response-evaluable participants. |
| Time to Response | Up to 3 Years | the time from the first dose of study drug until the first documentation of irCR or irPR, as related to current database lock date or most current tumor measurement |
| Duration of Response | from the first documented response (irCR or irPR) until progression or death | the time from the first documented response (irCR or irPR) until progression or death, whichever occurs first. For participants who did not progress or die, duration of response will be censored on the date of the last tumor assessment. |
| Progression Free Survival | 156 weeks | the time from the first dose to the first observation of disease progression or death due to any cause. If a participant has not progressed or died at the time of analysis, PFS will be censored on the date of the last disease assessment. Participants who did not have any on-study tumor assessments and did not die will be censored on the date of the first dose of study medication. |
| Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Up to 3 years | Serum samples will be collected to evaluate the development of antibodies to BMS-936558 and to ipilimumab. |
| Peak and Trough Concentrations | Up to 64 Weeks | The peak and trough concentrations of BMS-936558 (MDX-1106) and ipilimumab in participants with quantifiable data |
Countries
United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
127 Randomized and Treated
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 0.3 mg/kg of BMS-936558 (MDX-1106) + 3 mg/kg of ipilimumab | 14 |
| Cohort 2 1 mg/kg of BMS-936558 (MDX-1106) + 3 mg/kg of ipilimumab | 17 |
| Cohort 2a 3 mg/kg of BMS-936558 (MDX-1106) + 1 mg/kg of ipilimumab | 16 |
| Cohort 3 3 mg/kg of BMS-936558 (MDX-1106) + 3 mg/kg of ipilimumab | 6 |
| Cohort 6 1mg/kg of BMS-936558 (MDX-1106) | 17 |
| Cohorot 7 3 mg/kg of BMS-936558 (MDX-1106) | 16 |
| Cohort 8 1 mg/kg of BMS-936558 (MDX-1106) in combination with 3 mg/kg of ipilimumab every 3 weeks for 4 doses | 41 |
| Total | 127 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 2a | Cohort 3 | Cohort 6 | Cohorot 7 | Cohort 8 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.9 Years STANDARD_DEVIATION 9.58 | 53.5 Years STANDARD_DEVIATION 14.14 | 59.1 Years STANDARD_DEVIATION 14.65 | 56.2 Years STANDARD_DEVIATION 11.99 | 63.9 Years STANDARD_DEVIATION 14.37 | 60.6 Years STANDARD_DEVIATION 17.56 | 55.2 Years STANDARD_DEVIATION 15.83 | 57.6 Years STANDARD_DEVIATION 13.78 |
| Age, Customized <65 Years | 11 Participants | 14 Participants | 10 Participants | 5 Participants | 7 Participants | 11 Participants | 32 Participants | 90 Participants |
| Age, Customized ≥ 65 Years | 3 Participants | 3 Participants | 6 Participants | 1 Participants | 10 Participants | 5 Participants | 9 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 17 Participants | 16 Participants | 6 Participants | 15 Participants | 16 Participants | 39 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 14 Participants | 17 Participants | 16 Participants | 6 Participants | 16 Participants | 16 Participants | 37 Participants | 122 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 4 Participants | 5 Participants | 8 Participants | 7 Participants | 23 Participants | 59 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 12 Participants | 1 Participants | 9 Participants | 9 Participants | 18 Participants | 68 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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 14 | 4 / 17 | 2 / 16 | 0 / 6 | 7 / 17 | 8 / 16 | 8 / 41 |
| other Total, other adverse events | 14 / 14 | 17 / 17 | 16 / 16 | 6 / 6 | 17 / 17 | 15 / 16 | 41 / 41 |
| serious Total, serious adverse events | 10 / 14 | 15 / 17 | 10 / 16 | 5 / 6 | 9 / 17 | 10 / 16 | 26 / 41 |
Outcome results
Primary
Laboratory Abnormalities: Specific Liver Tests
Number of Participants with On-Treatment Laboratory Abnormalities in Specific Liver Tests Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 3 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 1 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 1 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 1 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 0 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 1 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 0 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 2 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 0 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 1 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 1 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 3 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 0 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 1 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 1 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 6 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 6 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 1 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 1 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 0 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 0 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 0 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 1 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 0 Participants |
| Only BMS | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 0 Participants |
| Only BMS | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Only BMS | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Only BMS | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 1 Participants |
| Only BMS | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 0 Participants |
| Only BMS | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 0 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 4 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 3 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 5 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 2 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 6 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 1 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 12 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 4 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 1 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 11 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 5 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 3 Participants |
| Total | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day | 1 Participants |
| Total | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 3xULN | 13 Participants |
| Total | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 10xULN | 5 Participants |
| Total | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 5xULN | 11 Participants |
| Total | Laboratory Abnormalities: Specific Liver Tests | ALT or AST > 20xULN | 4 Participants |
| Total | Laboratory Abnormalities: Specific Liver Tests | Total Bilirubin (Tbili) > 2xULN | 3 Participants |
Primary
Laboratory Abnormalities: Specific Thyroid Tests
Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 5 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 7 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 3 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 2 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 3 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 3 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 3 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 1 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 7 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 6 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 9 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 6 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 3 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 9 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 6 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 7 Participants |
| Cohort 2 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 7 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 7 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 7 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 7 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 5 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 7 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 7 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 6 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 3 Participants |
| Cohort 2a | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 3 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 2 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 3 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 3 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 2 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 3 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 1 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 2 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 3 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 25 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 17 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 26 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 11 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 18 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 17 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 20 Participants |
| Any BMS and Ipi Combo | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 20 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 4 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 2 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 3 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 4 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 3 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 4 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 4 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 2 Participants |
| Cohort 6 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 3 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 1 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 1 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 3 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 1 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohorot 7 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 1 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 7 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 3 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 3 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 5 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 4 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 7 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 5 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 2 Participants |
| Only BMS | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 8 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 14 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 8 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 8 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 5 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 11 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 14 Participants |
| Cohort 8 | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 6 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 23 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 33 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 34 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 23 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 28 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 19 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 34 Participants |
| Any BMS/Ipi | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 34 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH ALL OTHER T3/T4 TEST ≥ LLN | 40 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH FT3/FT4 TEST MISSING | 0 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN | 33 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH TSH >= LLN AT BASELINE | 37 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN with TSH≤ ULN @ Baseline | 27 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN | 39 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN | 41 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH AT LEAST ONE T3/T4 TEST < LLN | 26 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH < LLN: WITH AT LEAST ONE T3/T4 TEST > ULN | 21 Participants |
| Total | Laboratory Abnormalities: Specific Thyroid Tests | TSH > ULN: WITH FT3/FT4 TEST MISSING | 0 Participants |
Primary
Number of Deaths
incidence of all cause and treatment related deaths
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Deaths | All Cause | 8 Participants |
| Cohort 1 | Number of Deaths | Treatment Related | 0 Participants |
| Cohort 2 | Number of Deaths | All Cause | 4 Participants |
| Cohort 2 | Number of Deaths | Treatment Related | 0 Participants |
| Cohort 2a | Number of Deaths | All Cause | 2 Participants |
| Cohort 2a | Number of Deaths | Treatment Related | 0 Participants |
| Cohort 3 | Number of Deaths | All Cause | 0 Participants |
| Cohort 3 | Number of Deaths | Treatment Related | 0 Participants |
| Any BMS and Ipi Combo | Number of Deaths | All Cause | 14 Participants |
| Any BMS and Ipi Combo | Number of Deaths | Treatment Related | 0 Participants |
| Cohort 6 | Number of Deaths | Treatment Related | 0 Participants |
| Cohort 6 | Number of Deaths | All Cause | 7 Participants |
| Cohorot 7 | Number of Deaths | Treatment Related | 0 Participants |
| Cohorot 7 | Number of Deaths | All Cause | 8 Participants |
| Only BMS | Number of Deaths | All Cause | 15 Participants |
| Only BMS | Number of Deaths | Treatment Related | 0 Participants |
| Cohort 8 | Number of Deaths | All Cause | 8 Participants |
| Cohort 8 | Number of Deaths | Treatment Related | 1 Participants |
| Any BMS/Ipi | Number of Deaths | All Cause | 22 Participants |
| Any BMS/Ipi | Number of Deaths | Treatment Related | 1 Participants |
| Total | Number of Deaths | All Cause | 37 Participants |
| Total | Number of Deaths | Treatment Related | 1 Participants |
Primary
Number of Participants With an Adverse Event (AE)
incidence of all cause and treatment related adverse events
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With an Adverse Event (AE) | All Cause | 14 Participants |
| Cohort 1 | Number of Participants With an Adverse Event (AE) | Treatment Related | 13 Participants |
| Cohort 2 | Number of Participants With an Adverse Event (AE) | All Cause | 17 Participants |
| Cohort 2 | Number of Participants With an Adverse Event (AE) | Treatment Related | 17 Participants |
| Cohort 2a | Number of Participants With an Adverse Event (AE) | All Cause | 16 Participants |
| Cohort 2a | Number of Participants With an Adverse Event (AE) | Treatment Related | 15 Participants |
| Cohort 3 | Number of Participants With an Adverse Event (AE) | All Cause | 6 Participants |
| Cohort 3 | Number of Participants With an Adverse Event (AE) | Treatment Related | 6 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Adverse Event (AE) | All Cause | 53 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Adverse Event (AE) | Treatment Related | 51 Participants |
| Cohort 6 | Number of Participants With an Adverse Event (AE) | Treatment Related | 15 Participants |
| Cohort 6 | Number of Participants With an Adverse Event (AE) | All Cause | 17 Participants |
| Cohorot 7 | Number of Participants With an Adverse Event (AE) | Treatment Related | 13 Participants |
| Cohorot 7 | Number of Participants With an Adverse Event (AE) | All Cause | 16 Participants |
| Only BMS | Number of Participants With an Adverse Event (AE) | All Cause | 33 Participants |
| Only BMS | Number of Participants With an Adverse Event (AE) | Treatment Related | 28 Participants |
| Cohort 8 | Number of Participants With an Adverse Event (AE) | All Cause | 41 Participants |
| Cohort 8 | Number of Participants With an Adverse Event (AE) | Treatment Related | 40 Participants |
| Any BMS/Ipi | Number of Participants With an Adverse Event (AE) | All Cause | 94 Participants |
| Any BMS/Ipi | Number of Participants With an Adverse Event (AE) | Treatment Related | 91 Participants |
| Total | Number of Participants With an Adverse Event (AE) | All Cause | 127 Participants |
| Total | Number of Participants With an Adverse Event (AE) | Treatment Related | 119 Participants |
Primary
Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation
incidence of all cause and treatment related adverse events which lead to discontinuation
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 2 Participants |
| Cohort 1 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 2 Participants |
| Cohort 2 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 8 Participants |
| Cohort 2 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 6 Participants |
| Cohort 2a | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 5 Participants |
| Cohort 2a | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 5 Participants |
| Cohort 3 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 1 Participants |
| Cohort 3 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 1 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 16 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 14 Participants |
| Cohort 6 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 2 Participants |
| Cohort 6 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 5 Participants |
| Cohorot 7 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 0 Participants |
| Cohorot 7 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 1 Participants |
| Only BMS | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 6 Participants |
| Only BMS | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 2 Participants |
| Cohort 8 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 13 Participants |
| Cohort 8 | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 11 Participants |
| Any BMS/Ipi | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 29 Participants |
| Any BMS/Ipi | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 25 Participants |
| Total | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | All Cause | 35 Participants |
| Total | Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation | Treatment Related | 27 Participants |
Primary
Number of Participants With a Serious Adverse Event (AE)
incidence of all cause and treatment related serious adverse events
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With a Serious Adverse Event (AE) | All Cause | 10 Participants |
| Cohort 1 | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 5 Participants |
| Cohort 2 | Number of Participants With a Serious Adverse Event (AE) | All Cause | 15 Participants |
| Cohort 2 | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 13 Participants |
| Cohort 2a | Number of Participants With a Serious Adverse Event (AE) | All Cause | 10 Participants |
| Cohort 2a | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 9 Participants |
| Cohort 3 | Number of Participants With a Serious Adverse Event (AE) | All Cause | 5 Participants |
| Cohort 3 | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 4 Participants |
| Any BMS and Ipi Combo | Number of Participants With a Serious Adverse Event (AE) | All Cause | 40 Participants |
| Any BMS and Ipi Combo | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 31 Participants |
| Cohort 6 | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 4 Participants |
| Cohort 6 | Number of Participants With a Serious Adverse Event (AE) | All Cause | 9 Participants |
| Cohorot 7 | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 4 Participants |
| Cohorot 7 | Number of Participants With a Serious Adverse Event (AE) | All Cause | 10 Participants |
| Only BMS | Number of Participants With a Serious Adverse Event (AE) | All Cause | 19 Participants |
| Only BMS | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 8 Participants |
| Cohort 8 | Number of Participants With a Serious Adverse Event (AE) | All Cause | 26 Participants |
| Cohort 8 | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 18 Participants |
| Any BMS/Ipi | Number of Participants With a Serious Adverse Event (AE) | All Cause | 66 Participants |
| Any BMS/Ipi | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 49 Participants |
| Total | Number of Participants With a Serious Adverse Event (AE) | All Cause | 85 Participants |
| Total | Number of Participants With a Serious Adverse Event (AE) | Treatment Related | 57 Participants |
Primary
Number of Participants With Select AEs
incidence of all cause and treatment related Adverse events in certain organ systems
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Select AEs | Skin | 12 Participants |
| Cohort 1 | Number of Participants With Select AEs | Endrocrine | 2 Participants |
| Cohort 1 | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 0 Participants |
| Cohort 1 | Number of Participants With Select AEs | Renal | 2 Participants |
| Cohort 1 | Number of Participants With Select AEs | Pulmonary | 1 Participants |
| Cohort 1 | Number of Participants With Select AEs | Gastrointestinal | 5 Participants |
| Cohort 1 | Number of Participants With Select AEs | Hepatic | 5 Participants |
| Cohort 2 | Number of Participants With Select AEs | Gastrointestinal | 7 Participants |
| Cohort 2 | Number of Participants With Select AEs | Renal | 1 Participants |
| Cohort 2 | Number of Participants With Select AEs | Endrocrine | 5 Participants |
| Cohort 2 | Number of Participants With Select AEs | Skin | 15 Participants |
| Cohort 2 | Number of Participants With Select AEs | Pulmonary | 2 Participants |
| Cohort 2 | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 1 Participants |
| Cohort 2 | Number of Participants With Select AEs | Hepatic | 6 Participants |
| Cohort 2a | Number of Participants With Select AEs | Endrocrine | 3 Participants |
| Cohort 2a | Number of Participants With Select AEs | Pulmonary | 1 Participants |
| Cohort 2a | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 1 Participants |
| Cohort 2a | Number of Participants With Select AEs | Skin | 15 Participants |
| Cohort 2a | Number of Participants With Select AEs | Gastrointestinal | 10 Participants |
| Cohort 2a | Number of Participants With Select AEs | Renal | 1 Participants |
| Cohort 2a | Number of Participants With Select AEs | Hepatic | 4 Participants |
| Cohort 3 | Number of Participants With Select AEs | Gastrointestinal | 4 Participants |
| Cohort 3 | Number of Participants With Select AEs | Skin | 4 Participants |
| Cohort 3 | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 0 Participants |
| Cohort 3 | Number of Participants With Select AEs | Endrocrine | 3 Participants |
| Cohort 3 | Number of Participants With Select AEs | Pulmonary | 0 Participants |
| Cohort 3 | Number of Participants With Select AEs | Renal | 1 Participants |
| Cohort 3 | Number of Participants With Select AEs | Hepatic | 3 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Pulmonary | 4 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Endrocrine | 13 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Gastrointestinal | 26 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Hepatic | 18 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Renal | 5 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Skin | 46 Participants |
| Any BMS and Ipi Combo | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 2 Participants |
| Cohort 6 | Number of Participants With Select AEs | Hepatic | 1 Participants |
| Cohort 6 | Number of Participants With Select AEs | Renal | 0 Participants |
| Cohort 6 | Number of Participants With Select AEs | Pulmonary | 0 Participants |
| Cohort 6 | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 1 Participants |
| Cohort 6 | Number of Participants With Select AEs | Endrocrine | 4 Participants |
| Cohort 6 | Number of Participants With Select AEs | Skin | 8 Participants |
| Cohort 6 | Number of Participants With Select AEs | Gastrointestinal | 3 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Skin | 10 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Gastrointestinal | 4 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Renal | 1 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 1 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Endrocrine | 1 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Pulmonary | 1 Participants |
| Cohorot 7 | Number of Participants With Select AEs | Hepatic | 1 Participants |
| Only BMS | Number of Participants With Select AEs | Hepatic | 2 Participants |
| Only BMS | Number of Participants With Select AEs | Pulmonary | 1 Participants |
| Only BMS | Number of Participants With Select AEs | Gastrointestinal | 7 Participants |
| Only BMS | Number of Participants With Select AEs | Renal | 1 Participants |
| Only BMS | Number of Participants With Select AEs | Skin | 18 Participants |
| Only BMS | Number of Participants With Select AEs | Endrocrine | 5 Participants |
| Only BMS | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 2 Participants |
| Cohort 8 | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 1 Participants |
| Cohort 8 | Number of Participants With Select AEs | Gastrointestinal | 20 Participants |
| Cohort 8 | Number of Participants With Select AEs | Endrocrine | 12 Participants |
| Cohort 8 | Number of Participants With Select AEs | Pulmonary | 2 Participants |
| Cohort 8 | Number of Participants With Select AEs | Skin | 34 Participants |
| Cohort 8 | Number of Participants With Select AEs | Hepatic | 8 Participants |
| Cohort 8 | Number of Participants With Select AEs | Renal | 1 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Skin | 80 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Renal | 6 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Pulmonary | 6 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Endrocrine | 25 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 3 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Gastrointestinal | 46 Participants |
| Any BMS/Ipi | Number of Participants With Select AEs | Hepatic | 26 Participants |
| Total | Number of Participants With Select AEs | Gastrointestinal | 53 Participants |
| Total | Number of Participants With Select AEs | Skin | 98 Participants |
| Total | Number of Participants With Select AEs | Renal | 7 Participants |
| Total | Number of Participants With Select AEs | Hepatic | 28 Participants |
| Total | Number of Participants With Select AEs | Pulmonary | 7 Participants |
| Total | Number of Participants With Select AEs | Hypersensitivity/Infusion Reaction | 5 Participants |
| Total | Number of Participants With Select AEs | Endrocrine | 30 Participants |
Secondary
Duration of Response
the time from the first documented response (irCR or irPR) until progression or death, whichever occurs first. For participants who did not progress or die, duration of response will be censored on the date of the last tumor assessment.
Time frame: from the first documented response (irCR or irPR) until progression or death
Population: All Treated Participants with a response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Response | NA Weeks |
| Cohort 2 | Duration of Response | 105 Weeks |
| Cohort 2a | Duration of Response | 66.3 Weeks |
| Cohort 3 | Duration of Response | 59.1 Weeks |
| Any BMS and Ipi Combo | Duration of Response | 105 Weeks |
| Cohort 6 | Duration of Response | 73.1 Weeks |
| Cohorot 7 | Duration of Response | 64.3 Weeks |
| Only BMS | Duration of Response | 73.1 Weeks |
| Cohort 8 | Duration of Response | NA Weeks |
| Any BMS/Ipi | Duration of Response | 105 Weeks |
| Total | Duration of Response | 105 Weeks |
Secondary
Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi)
Serum samples will be collected to evaluate the development of antibodies to BMS-936558 and to ipilimumab.
Time frame: Up to 3 years
Population: All Treated Participants with baseline and at least one post baseline assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 6 Participants |
| Cohort 1 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 0 Participants |
| Cohort 1 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 12 Participants |
| Cohort 1 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 1 Participants |
| Cohort 1 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 7 Participants |
| Cohort 1 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 1 Participants |
| Cohort 2 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 10 Participants |
| Cohort 2 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 1 Participants |
| Cohort 2 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 0 Participants |
| Cohort 2 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 17 Participants |
| Cohort 2 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 1 Participants |
| Cohort 2 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 7 Participants |
| Cohort 2a | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 0 Participants |
| Cohort 2a | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 2 Participants |
| Cohort 2a | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 12 Participants |
| Cohort 2a | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 4 Participants |
| Cohort 2a | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 16 Participants |
| Cohort 2a | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 0 Participants |
| Cohort 3 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 5 Participants |
| Cohort 3 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 1 Participants |
| Cohort 3 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 0 Participants |
| Cohort 3 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 0 Participants |
| Cohort 3 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 5 Participants |
| Cohort 3 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 0 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 1 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 4 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 50 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 2 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 31 Participants |
| Any BMS and Ipi Combo | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 20 Participants |
| Cohort 6 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 11 Participants |
| Cohort 6 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 1 Participants |
| Cohort 6 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 0 Participants |
| Cohort 6 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 4 Participants |
| Cohort 6 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 1 Participants |
| Cohort 6 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 13 Participants |
| Cohorot 7 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 10 Participants |
| Cohorot 7 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 0 Participants |
| Cohorot 7 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 1 Participants |
| Cohorot 7 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 1 Participants |
| Cohorot 7 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 0 Participants |
| Cohorot 7 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 11 Participants |
| Only BMS | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 23 Participants |
| Only BMS | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 2 Participants |
| Only BMS | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 5 Participants |
| Only BMS | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 1 Participants |
| Only BMS | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 22 Participants |
| Only BMS | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 0 Participants |
| Cohort 8 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 10 Participants |
| Cohort 8 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 1 Participants |
| Cohort 8 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 1 Participants |
| Cohort 8 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 25 Participants |
| Cohort 8 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 1 Participants |
| Cohort 8 | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 31 Participants |
| Any BMS/Ipi | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 5 Participants |
| Any BMS/Ipi | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 2 Participants |
| Any BMS/Ipi | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 81 Participants |
| Any BMS/Ipi | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 3 Participants |
| Any BMS/Ipi | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 30 Participants |
| Any BMS/Ipi | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 56 Participants |
| Total | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (ipi) | 104 Participants |
| Total | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (nivo) | 6 Participants |
| Total | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (nivo) | 35 Participants |
| Total | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | Baseline ADA Positive (ipi) | 3 Participants |
| Total | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Positive (ipi) | 4 Participants |
| Total | Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) | ADA Negative (nivo) | 78 Participants |
Secondary
Objective Response Rate
the total number of participants whose best overall response (BOR) is either irCR or irPR divided by the total number of response-evaluable participants.
Time frame: Up to 3 years
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Objective Response Rate | 21 Percentage of Participants |
| Cohort 2 | Objective Response Rate | 47 Percentage of Participants |
| Cohort 2a | Objective Response Rate | 50 Percentage of Participants |
| Cohort 3 | Objective Response Rate | 50 Percentage of Participants |
| Any BMS and Ipi Combo | Objective Response Rate | 42 Percentage of Participants |
| Cohort 6 | Objective Response Rate | 53 Percentage of Participants |
| Cohorot 7 | Objective Response Rate | 19 Percentage of Participants |
| Only BMS | Objective Response Rate | 36 Percentage of Participants |
| Cohort 8 | Objective Response Rate | 44 Percentage of Participants |
| Any BMS/Ipi | Objective Response Rate | 43 Percentage of Participants |
| Total | Objective Response Rate | 41 Percentage of Participants |
Secondary
Peak and Trough Concentrations
The peak and trough concentrations of BMS-936558 (MDX-1106) and ipilimumab in participants with quantifiable data
Time frame: Up to 64 Weeks
Population: All Treated Participants with quantifiable data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Peak and Trough Concentrations | Ipi Trough (Cmin) | 9.7 ug/mL | Geometric Coefficient of Variation 33.7 |
| Cohort 1 | Peak and Trough Concentrations | Nivo Peak (Cmax) | 6.5 ug/mL | Geometric Coefficient of Variation 17.2 |
| Cohort 1 | Peak and Trough Concentrations | Ipi Peak (Cmax) | 63.9 ug/mL | Geometric Coefficient of Variation 17.7 |
| Cohort 1 | Peak and Trough Concentrations | Nivo Trough (Cmin) | 1.5 ug/mL | Geometric Coefficient of Variation 44.9 |
| Cohort 2 | Peak and Trough Concentrations | Ipi Peak (Cmax) | 68.5 ug/mL | Geometric Coefficient of Variation 20.4 |
| Cohort 2 | Peak and Trough Concentrations | Ipi Trough (Cmin) | 11.9 ug/mL | Geometric Coefficient of Variation 29.5 |
| Cohort 2 | Peak and Trough Concentrations | Nivo Peak (Cmax) | 21.5 ug/mL | Geometric Coefficient of Variation 17.9 |
| Cohort 2 | Peak and Trough Concentrations | Nivo Trough (Cmin) | 2.6 ug/mL | Geometric Coefficient of Variation 94.4 |
| Cohort 2a | Peak and Trough Concentrations | Nivo Trough (Cmin) | 27.7 ug/mL | Geometric Coefficient of Variation 23.9 |
| Cohort 2a | Peak and Trough Concentrations | Nivo Peak (Cmax) | 49.8 ug/mL | Geometric Coefficient of Variation 24.7 |
| Cohort 2a | Peak and Trough Concentrations | Ipi Trough (Cmin) | 3.6 ug/mL | Geometric Coefficient of Variation 30.4 |
| Cohort 2a | Peak and Trough Concentrations | Ipi Peak (Cmax) | 19.8 ug/mL | Geometric Coefficient of Variation 40.6 |
| Cohort 3 | Peak and Trough Concentrations | Nivo Peak (Cmax) | 63.4 ug/mL | Geometric Coefficient of Variation 18 |
| Cohort 3 | Peak and Trough Concentrations | Ipi Peak (Cmax) | 63.2 ug/mL | Geometric Coefficient of Variation 24.2 |
| Cohort 3 | Peak and Trough Concentrations | Ipi Trough (Cmin) | 9.2 ug/mL | Geometric Coefficient of Variation 34.4 |
| Cohort 3 | Peak and Trough Concentrations | Nivo Trough (Cmin) | 23.9 ug/mL | Geometric Coefficient of Variation 37.5 |
| Cohort 6 | Peak and Trough Concentrations | Nivo Peak (Cmax) | 20.5 ug/mL | Geometric Coefficient of Variation 64.5 |
| Cohort 6 | Peak and Trough Concentrations | Nivo Trough (Cmin) | 13.2 ug/mL | Geometric Coefficient of Variation 40.9 |
| Cohorot 7 | Peak and Trough Concentrations | Nivo Trough (Cmin) | 53.1 ug/mL | Geometric Coefficient of Variation 49.8 |
| Cohorot 7 | Peak and Trough Concentrations | Nivo Peak (Cmax) | 97.7 ug/mL | Geometric Coefficient of Variation 52.5 |
| Cohort 8 | Peak and Trough Concentrations | Ipi Peak (Cmax) | 63.5 ug/mL | Geometric Coefficient of Variation 31.5 |
| Cohort 8 | Peak and Trough Concentrations | Nivo Trough (Cmin) | 5.9 ug/mL | Geometric Coefficient of Variation 49.3 |
| Cohort 8 | Peak and Trough Concentrations | Nivo Peak (Cmax) | 18.1 ug/mL | Geometric Coefficient of Variation 38.1 |
| Cohort 8 | Peak and Trough Concentrations | Ipi Trough (Cmin) | 9.8 ug/mL | Geometric Coefficient of Variation 43.7 |
Secondary
Progression Free Survival
the time from the first dose to the first observation of disease progression or death due to any cause. If a participant has not progressed or died at the time of analysis, PFS will be censored on the date of the last disease assessment. Participants who did not have any on-study tumor assessments and did not die will be censored on the date of the first dose of study medication.
Time frame: 156 weeks
Population: All Treated Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression Free Survival | 12.50 Weeks |
| Cohort 2 | Progression Free Survival | 64.40 Weeks |
| Cohort 2a | Progression Free Survival | 58.40 Weeks |
| Cohort 3 | Progression Free Survival | 33.55 Weeks |
| Cohort 6 | Progression Free Survival | 24.60 Weeks |
| Cohorot 7 | Progression Free Survival | 12.15 Weeks |
| Cohort 8 | Progression Free Survival | 37.10 Weeks |
Secondary
Time to Response
the time from the first dose of study drug until the first documentation of irCR or irPR, as related to current database lock date or most current tumor measurement
Time frame: Up to 3 Years
Population: All Treated Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Response | 11.9 Weeks |
| Cohort 2 | Time to Response | 11.9 Weeks |
| Cohort 2a | Time to Response | 11.9 Weeks |
| Cohort 3 | Time to Response | 12.3 Weeks |
| Any BMS and Ipi Combo | Time to Response | 11.9 Weeks |
| Cohort 6 | Time to Response | 8 Weeks |
| Cohorot 7 | Time to Response | 15.7 Weeks |
| Only BMS | Time to Response | 9.6 Weeks |
| Cohort 8 | Time to Response | 12.1 Weeks |
| Any BMS/Ipi | Time to Response | 12 Weeks |
| Total | Time to Response | 12 Weeks |