CANCER,NOS
Conditions
Brief summary
To assess the safety and tolerability and preliminary anti-tumor activity of lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558) and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination. In addition, to assess the combinations of lirilumab and nivolumab or lirilumab and nivolumab plus ipilimumab (BMS-734016) in subjects with advanced (metastatic and/or unresectable) refractory solid tumors.
Interventions
DRUGLirilumab
Specified dose on specified days.
DRUGNivolumab
Specified dose on specified days.
DRUGIpilimumab
Specified dose on specified days.
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
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: * During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen * During cohort expansion, subjects with various solid tumors that have received at least one and no more than 5 prior treatment regimens * Subjects must have measurable disease * Subject must consent to provide previously collected tumor tissue * Women and men ≥18 years of age with performance status of 0 or 1 * At least 4 weeks since any previous treatment for cancer
Exclusion criteria
* Active or chronic autoimmune diseases * Uncontrolled or significant cardiovascular disease * Chronic hepatitis (except for subjects with hepatocellular carcinoma) * Active infection * Active Central nervous system (CNS) metastases * Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome((HIV/AIDS) * Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma) Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. |
| Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. |
| Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | Number of participants that experienced an AE leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. |
| The Number of Participant Deaths in the Study - Parts 1, 2 and 5 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | The number of participants who died. |
| Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | Number of participants that experienced a clinical laboratory test abnormality, including hematology and serum chemistry, and thyroid panel abnormalities. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Laboratory tests are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 3 is severe, and Grade 4 is life threatening. Baseline is defined as the last non-missing measurement prior to the first dosing date and time. |
| Objective Response Rate (ORR) | From first dose up to approximately 2.5 years | Objective Response Rate (ORR) is defined as the percent of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR for a participant was derived using investigator-provided tumor measurements per RECIST v1.1. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate (PFSR) at 6 Months - Part 3 | At 6 months after first dose | Percentage of treated participants remaining progression free and surviving at 6 months. For those participants who remain alive and have not progressed, PFS will be censored on the date of the last tumor assessment. Progression is defined as At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Clinical deterioration in the absence of radiographic evidence is not considered progression. |
| Number of Participants With Adverse Events (AEs) - Part 3 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. |
| Number of Participants With Serious Adverse Events (SAEs) - Part 3 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. |
| Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | Number of participants that experienced an AE leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. |
| The Number of Participant Deaths in the Study - Part 3 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | The number of participants who died. |
| Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years) | Number of participants that experienced a clinical laboratory test abnormality, including hematology and serum chemistry, and thyroid panel abnormalities. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Laboratory tests are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 3 is severe, and Grade 4 is life threatening. Baseline is defined as the last non-missing measurement prior to the first dosing date and time. |
| Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | From first dose to 100 days after last dose (up to approximately 126 weeks) | Number of participants observed as ADA positive at baseline, ADA positive (post-baseline), and ADA negative (post-baseline). Baseline is defined as the last sample before initiation of treatment Baseline ADA Positive Participant: A participant with baseline ADA positive sample. ADA Positive Participant: Participant with \>=1 ADA +ve sample relative to baseline (baseline ADA -ve, or ADA titer \>= 9-fold for Lirilumab and \>= 4-fold for Nivolumab relative to baseline +ve titer) at any time after first dose during the defined observation time period. ADA Negative Participant: A participant with no ADA positive sample after the initiation of treatment. |
| The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | Pre-dose Day 1 (Cycles 1 ,3 ,5, 7, 9), Pre-dose Day 29 (Cycle 1, 2) | The number of participants with 1% or 5% PD-L1 expression in the tumor cell membrane. Participants are considered positive if they show \>=1% or \>= 5% PD-L1 expression in the tumor cell membrane and negative if they show \< 1% or \< 5%. PD-L1 expression is defined as the percent of tumor cells demonstrating plasma membrane PDL1 staining of any intensity. PD-L1 will be evaluated by immunohistochemistry (IHC). PD-L1 status at pretreatment is considered positive if any pretreatment sample is positive. PDL1= programmed cell death ligand 1 |
| Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Disease Control Rate (DCR) - Part 3 | From first dose up to approximately 2.5 years | Disease Control Rate (DCR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. All participants will be monitored by radiographic assessment every 8 weeks from first dose to Week 48, and every 12 weeks thereafter until PD or treatment discontinuation. |
| Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. |
| Half-life (T-HALF) - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. |
| Clearance Per Time (CLT) - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Ctrough - Parts 1, 2 and 5 (Nivo) | 336 hours post dose on cycle 1 day 1 (cycle 1 day 15) and pre-dose and end of infusion on cycle 2 day 29. | Pharmacokinetics of nivolumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. AUC(INF) was based on appropriate characterization of the elimination phase of the concentration versus time curve, which was unable to be performed due to limited sampling in this study. |
| Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. VZ was based on appropriate characterization of the elimination phase of the concentration versus time curve, which was unable to be performed due to limited sampling in this study. |
| End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Ctrough - Parts 1, 2 and 5 (Liri) | Pre-dose on cycle 1 day 29 and Pre-dose and end of infusion on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29. | Pharmacokinetics of nivolumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29. | Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below. |
| Median Duration of Response (mDOR) - Parts 3 and 5 | From first dose to the date of the first documented tumor progression as determined or death due to any cause, whichever occurs first. (Up to approximately 2.5 years) | DOR is defined as the time from the date of first response (CR or PR) to the date of first objectively documented tumor progression as determined using RECIST v1.1 or death due to any cause, whichever occurs first. Participant who remain alive and have not progressed were censored on the date of their last evaluable tumor assessment. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the subsequent anticancer therapy. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Median Time to Response (mTTR) - Part 3 | From date of first dose of study medication to the date of the first documented objective response (up to approximately 2.5 years) | TTR is defined as the time from the first dosing date to the date of the first documented objective response (CR or PR). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | From first dose until progressive disease (PD) or treatment discontinuation, whichever occurs earlier. (Up to approximately 2.5 years) | Depth of response is defined as the target tumor burden percent change from baseline at nadir for each participant as measured by the number of participants with \>= 50% and \>= 80% tumor reduction. Tumor assessments are performed every 8 weeks from first dose date for 48 weeks, and then every 12 weeks thereafter until progressive disease (PD) or treatment discontinuation, whichever occurs earlier. |
| Overall Survival (OS) - Part 3 | From date of first dose of study medication to the date of death for any cause. (Up to approximately 2.5 years) | Overall Survival (OS) is defined as the time from date of first dose of study medication to the date of death for any cause. A participant who has not died will be censored at last known date alive. OS for a participant who initiated new cancer treatment, will also be censored at the date of the new treatment initiation. Estimated by Kaplan-Meier Method. |
| Progression Free Survival (PFS) - Part 3 | From first dose to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. (Up to approximately 2.5 years) | PFS is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Participants who died without a reported prior progression was considered to have progressed on the date of their death. Participants alive with no progression were censored on the last evaluable tumor assessment date. Participants who started subsequent therapy with no prior progression were censored at the last evaluable tumor assessment prior to initiation of the subsequent therapy. Participants with no post-baseline tumor assessment and alive were censored on the date of first dose. Progression is defined as At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Clinical deterioration in the absence of radiographic evidence is not considered progression. |
Countries
Canada, France, Italy, Spain, Switzerland, United States
Participant flow
Pre-assignment details
Part 4 and Part 6 of the study were removed from the protocol study design prior to enrolling any subjects.
Participants by arm
| Arm | Count |
|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 Participants receive Lirilumab 0.1 mg/kg every 4 weeks (Q4W) and Nivolumab 3 mg/kg every 2 weeks (Q2W) for twelve 8-week treatment cycles. | 4 |
| Part 1/2: Liri 0.3 + Nivo 3 Participants receive Lirilumab 0.3 mg/kg every 4 weeks (Q4W) and Nivolumab 3 mg/kg every 2 weeks (Q2W) for twelve 8-week treatment cycles. | 16 |
| Part 1/2: Liri 1 + Nivo 3 Participants receive Lirilumab 1 mg/kg every 4 weeks (Q4W) and Nivolumab 3 mg/kg every 2 weeks (Q2W) for twelve 8-week treatment cycles. | 15 |
| Part 1/2: Liri 3 + Nivo 3 Participants receive Lirilumab 3 mg/kg every 4 weeks (Q4W) and Nivolumab 3 mg/kg every 2 weeks (Q2W) for twelve 8-week treatment cycles. | 287 |
| Part 3: PBO + Nivo 240 Participants receive Placebo every 4 weeks (Q4W) and a flat dose of nivolumab monotherapy (240mg) every 2 weeks (Q2W) for 8-week cycles until progressive disease. | 2 |
| Part 3: Liri 240 + Nivo 240 Participants receive Lirilumab 240 mg every 4 weeks (Q4W) and a flat dose of nivolumab 240 mg every 2 weeks (Q2W) for 8-week cycles until progressive disease. | 3 |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 Participants receive Lirilumab 3 mg/kg IV every 4 weeks (Q4W), Nivolumab 3 mg/kg IV every 2 weeks (Q2W), and Ipilimumab 1 mg/kg IV every 6 weeks (Q6W) for 12-week cycles until progressive disease | 10 |
| Total | 337 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event unrelated to drug | 0 | 0 | 3 | 21 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Disease progression | 3 | 5 | 5 | 204 | 1 | 3 | 5 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Maximum clinical benefit | 0 | 1 | 1 | 3 | 0 | 0 | 0 |
| Overall Study | No longer meets study criteria | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other reason | 0 | 0 | 0 | 3 | 1 | 0 | 0 |
| Overall Study | Participant request to stop therapy | 0 | 1 | 0 | 6 | 0 | 0 | 0 |
| Overall Study | Participant withdrew consent | 0 | 1 | 0 | 8 | 0 | 0 | 0 |
| Overall Study | Poor/non-comliance | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study drug toxicity | 1 | 1 | 1 | 15 | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Part 1/2 Liri 0.1 + Nivo 3 | Part 1/2: Liri 0.3 + Nivo 3 | Part 1/2: Liri 1 + Nivo 3 | Part 1/2: Liri 3 + Nivo 3 | Part 3: PBO + Nivo 240 | Part 3: Liri 240 + Nivo 240 | Part 5: Liri 3 + Nivo 3 + Ipi 1 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.3 Years STANDARD_DEVIATION 12.09 | 58.1 Years STANDARD_DEVIATION 13.11 | 58.7 Years STANDARD_DEVIATION 16.85 | 59.7 Years STANDARD_DEVIATION 11.37 | 65.5 Years STANDARD_DEVIATION 10.61 | 55.3 Years STANDARD_DEVIATION 21.08 | 67.1 Years STANDARD_DEVIATION 10.4 | 59.7 Years STANDARD_DEVIATION 11.81 |
| Age, Customized < 65 years old | 4 Participants | 10 Participants | 9 Participants | 184 Participants | 1 Participants | 2 Participants | 5 Participants | 215 Participants |
| Age, Customized >= 65 years old | 0 Participants | 6 Participants | 6 Participants | 103 Participants | 1 Participants | 1 Participants | 5 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 15 Participants | 15 Participants | 175 Participants | 1 Participants | 1 Participants | 8 Participants | 219 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 106 Participants | 1 Participants | 2 Participants | 2 Participants | 112 Participants |
| Race/Ethnicity, Customized American Indian / Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 29 Participants | 0 Participants | 0 Participants | 0 Participants | 29 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 16 Participants | 15 Participants | 237 Participants | 2 Participants | 3 Participants | 10 Participants | 287 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants | 80 Participants | 1 Participants | 1 Participants | 1 Participants | 97 Participants |
| Sex: Female, Male Male | 2 Participants | 11 Participants | 8 Participants | 207 Participants | 1 Participants | 2 Participants | 9 Participants | 240 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 | 2 / 4 | 7 / 16 | 5 / 15 | 219 / 287 | 1 / 2 | 3 / 3 | 5 / 10 |
| other Total, other adverse events | 4 / 4 | 16 / 16 | 15 / 15 | 271 / 287 | 2 / 2 | 3 / 3 | 10 / 10 |
| serious Total, serious adverse events | 1 / 4 | 8 / 16 | 9 / 15 | 205 / 287 | 2 / 2 | 3 / 3 | 7 / 10 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5
Number of participants that experienced an AE leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Parts 1, 2 and 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 | 4 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 | 49 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 | 5 Participants |
Primary
Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Parts 1, 2 and 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 | 4 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 | 16 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 | 15 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 | 284 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 | 10 Participants |
Primary
Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5
Number of participants that experienced a clinical laboratory test abnormality, including hematology and serum chemistry, and thyroid panel abnormalities. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Laboratory tests are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 3 is severe, and Grade 4 is life threatening. Baseline is defined as the last non-missing measurement prior to the first dosing date and time.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants with available laboratory test measurements. Pre-specified for data to be collected only in Parts 1, 2 and 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | pH, Arterial Blood - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Fasting Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 4 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 3 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 3 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Fasting Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Ionized - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Ionized - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 3 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 3 | 3 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 3 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 4 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 3 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 3 | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 3 | 3 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 3 | 2 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 4 | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 3 | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 3 | 4 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 3 | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 3 | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 4 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 3 | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatine Kinase (CK) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Fasting Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Corrected - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Corrected - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Ionized - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 4 | 3 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Ionized - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 3 | 6 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 4 | 4 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatine Kinase (CK) - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 3 | 1 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Fibrinogen - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 3 | 18 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 4 | 7 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Turbidimetric Assay) - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Turbidimetric Assay) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 3 | 64 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 4 | 9 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 3 | 6 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 3 | 1 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 4 | 1 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 3 | 24 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | pH, Arterial Blood - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | pH, Arterial Blood - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 3 | 2 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 3 | 10 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Fasting Serum - Grade 3 | 1 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | G-Glutamyl Transferase (GGT) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 4 | 1 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 3 | 3 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 4 | 3 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | G-Glutamyl Transferase (GGT) - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 3 | 26 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 3 | 8 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 4 | 1 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 3 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 3 | 2 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 3 | 6 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 3 | 4 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Fibrinogen - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 3 | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatine Kinase (CK) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Corrected - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatine Kinase (CK) - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Fasting Serum - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Fibrinogen - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Potassium, Serum - Grade 4 | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Corrected - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Total - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Leukocytes - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Aspartate Aminotransferase (AST) - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 3 | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Magnesium, Serum - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lymphocytes (Absolute) - Grade 3 | 4 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alkaline Phosphatase (ALP) - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Sodium Serum - Grade 3 | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Ionized - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Bilirubin, Total - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Amylase, Total - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Platelet Count - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Fibrinogen - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Calcium, Ionized - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Lipase, Total (Colorimetric Assay) - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Absolute Neutrophil Count - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Creatinine - Grade 3 | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Glucose, Fasting Serum - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Phosphorus, Inorganic - Grade 3 | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | APTT - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Neutrophils (Absolute) - Grade 3 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Hemoglobin - Grade 4 | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 | Albumin - Grade 4 | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Parts 1, 2 and 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 | 8 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 | 9 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 | 205 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 | 7 Participants |
Primary
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the percent of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR for a participant was derived using investigator-provided tumor measurements per RECIST v1.1. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose up to approximately 2.5 years
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Objective Response Rate (ORR) | 25.0 Percentage of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Objective Response Rate (ORR) | 37.5 Percentage of participants |
| Part 1/2: Liri 1 + Nivo 3 | Objective Response Rate (ORR) | 40.0 Percentage of participants |
| Part 1/2: Liri 3 + Nivo 3 | Objective Response Rate (ORR) | 14.6 Percentage of participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Objective Response Rate (ORR) | 50.0 Percentage of participants |
| Part 3: Liri 240 + Nivo 240 | Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Objective Response Rate (ORR) | 0 Percentage of participants |
Primary
The Number of Participant Deaths in the Study - Parts 1, 2 and 5
The number of participants who died.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Parts 1, 2 and 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participant Deaths in the Study - Parts 1, 2 and 5 | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participant Deaths in the Study - Parts 1, 2 and 5 | 7 Participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participant Deaths in the Study - Parts 1, 2 and 5 | 5 Participants |
| Part 1/2: Liri 3 + Nivo 3 | The Number of Participant Deaths in the Study - Parts 1, 2 and 5 | 219 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | The Number of Participant Deaths in the Study - Parts 1, 2 and 5 | 5 Participants |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. VZ was based on appropriate characterization of the elimination phase of the concentration versus time curve, which was unable to be performed due to limited sampling in this study.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data samples. Due to limited sampling in this study, data was not collected. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5 | Cycle 1 | — |
| Unknown | Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5 | Cycle 2 | — |
Secondary
Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. AUC(INF) was based on appropriate characterization of the elimination phase of the concentration versus time curve, which was unable to be performed due to limited sampling in this study.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data samples. Due to limited sampling in this study, data was not collected. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5 | Cycle 1 | — |
| Unknown | Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5 | Cycle 2 | — |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 1 | 360903.09 hour*ng/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 2 | 569516.79 hour*ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 1 | 734836.53 hour*ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 2 | 1367259.80 hour*ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 2 | 6547184.03 hour*ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 1 | 4462883.03 hour*ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 1 | 9647500.52 hour*ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 2 | 11731186.91 hour*ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 1 | 8819119.61 hour*ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 | Cycle 2 | 9958714.89 hour*ng/mL |
Secondary
Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 1 | 366418.73 hour*ng/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 2 | 569516.79 hour*ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 2 | 1726615.52 hour*ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 1 | 1155363.50 hour*ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 2 | 6712959.58 hour*ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 1 | 4462883.03 hour*ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 2 | 18504162.18 hour*ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 1 | 11418017.10 hour*ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 | Cycle 1 | 10843715.48 hour*ng/mL |
Secondary
Clearance Per Time (CLT) - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Clearance Per Time (CLT) - Parts 1, 2 and 5 | 0.01 liter per hour |
| Part 1/2: Liri 0.3 + Nivo 3 | Clearance Per Time (CLT) - Parts 1, 2 and 5 | 0.01 liter per hour |
| Part 1/2: Liri 1 + Nivo 3 | Clearance Per Time (CLT) - Parts 1, 2 and 5 | 0.01 liter per hour |
| Part 1/2: Liri 3 + Nivo 3 | Clearance Per Time (CLT) - Parts 1, 2 and 5 | 0.01 liter per hour |
Secondary
Ctrough - Parts 1, 2 and 5 (Liri)
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose on cycle 1 day 29 and Pre-dose and end of infusion on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 29 | 192.29 ng/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 327.50 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 29 | 521.28 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 1069.84 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 29 | 2572.90 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 4592.95 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 10865.91 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 29 | 6195.08 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 29 | 5190.00 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Ctrough - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 19100.00 ng/mL |
Secondary
Ctrough - Parts 1, 2 and 5 (Nivo)
Pharmacokinetics of nivolumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: 336 hours post dose on cycle 1 day 1 (cycle 1 day 15) and pre-dose and end of infusion on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of nivolumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 55.67 μg/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 15 | 19.15 μg/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 62.18 μg/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 15 | 20.14 μg/mL |
| Part 1/2: Liri 1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 15 | 21.36 μg/mL |
| Part 1/2: Liri 1 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 71.31 μg/mL |
| Part 1/2: Liri 3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 15 | 15.81 μg/mL |
| Part 1/2: Liri 3 + Nivo 3 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 50.07 μg/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 62.62 μg/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Ctrough - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 15 | 17.30 μg/mL |
Secondary
Disease Control Rate (DCR) - Part 3
Disease Control Rate (DCR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. All participants will be monitored by radiographic assessment every 8 weeks from first dose to Week 48, and every 12 weeks thereafter until PD or treatment discontinuation.
Time frame: From first dose up to approximately 2.5 years
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Disease Control Rate (DCR) - Part 3 | 50.0 Percentage of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Disease Control Rate (DCR) - Part 3 | 33.3 Percentage of participants |
Secondary
End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri)
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 1 | 2223.10 ng/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 2277.39 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 1 | 6434.65 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 7286.95 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 1 | 22250.96 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 25185.06 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 65874.20 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 1 | 45163.87 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 1 Day 1 | 65333.91 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) | Cycle 2 Day 29 | 81600.00 ng/mL |
Secondary
End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo)
Pharmacokinetics of nivolumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29.
Population: All treated participants who received at least 1 dose of nivolumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 1 | 63.16 μg/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 104.47 μg/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 1 | 66.33 μg/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 114.89 μg/mL |
| Part 1/2: Liri 1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 1 | 66.16 μg/mL |
| Part 1/2: Liri 1 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 116.08 μg/mL |
| Part 1/2: Liri 3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 99.75 μg/mL |
| Part 1/2: Liri 3 + Nivo 3 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 1 | 52.48 μg/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 1 Day 1 | 44.75 μg/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) | Cycle 2 Day 29 | 115.37 μg/mL |
Secondary
Half-life (T-HALF) - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data.
Time frame: Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Half-life (T-HALF) - Parts 1, 2 and 5 | 383.96 hour | Standard Deviation 235.421 |
| Part 1/2: Liri 0.3 + Nivo 3 | Half-life (T-HALF) - Parts 1, 2 and 5 | 273.89 hour | Standard Deviation 234.588 |
| Part 1/2: Liri 1 + Nivo 3 | Half-life (T-HALF) - Parts 1, 2 and 5 | 515.07 hour | Standard Deviation 361.525 |
| Part 1/2: Liri 3 + Nivo 3 | Half-life (T-HALF) - Parts 1, 2 and 5 | 281.31 hour | Standard Deviation 237.236 |
Secondary
Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 2 | 2277.39 ng/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 1 | 2223.10 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 1 | 6509.35 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 2 | 7286.95 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 2 | 25623.89 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 1 | 22250.96 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 1 | 52034.18 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 2 | 69224.70 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 1 | 65333.91 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 | Cycle 2 | 81600.00 ng/mL |
Secondary
Median Duration of Response (mDOR) - Parts 3 and 5
DOR is defined as the time from the date of first response (CR or PR) to the date of first objectively documented tumor progression as determined using RECIST v1.1 or death due to any cause, whichever occurs first. Participant who remain alive and have not progressed were censored on the date of their last evaluable tumor assessment. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the subsequent anticancer therapy. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose to the date of the first documented tumor progression as determined or death due to any cause, whichever occurs first. (Up to approximately 2.5 years)
Population: All treated participants with a confirmed BOR of CR or PR. Pre-specified for data to be collected only in Parts 3 and 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Median Duration of Response (mDOR) - Parts 3 and 5 | NA weeks |
Secondary
Median Time to Response (mTTR) - Part 3
TTR is defined as the time from the first dosing date to the date of the first documented objective response (CR or PR). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of first dose of study medication to the date of the first documented objective response (up to approximately 2.5 years)
Population: All treated participants with a confirmed BOR of CR or PR. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Median Time to Response (mTTR) - Part 3 | 8.10 Weeks |
Secondary
Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3
Number of participants that experienced an AE leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3 | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs) - Part 3
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Adverse Events (AEs) - Part 3 | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Adverse Events (AEs) - Part 3 | 3 Participants |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5
Number of participants observed as ADA positive at baseline, ADA positive (post-baseline), and ADA negative (post-baseline). Baseline is defined as the last sample before initiation of treatment Baseline ADA Positive Participant: A participant with baseline ADA positive sample. ADA Positive Participant: Participant with \>=1 ADA +ve sample relative to baseline (baseline ADA -ve, or ADA titer \>= 9-fold for Lirilumab and \>= 4-fold for Nivolumab relative to baseline +ve titer) at any time after first dose during the defined observation time period. ADA Negative Participant: A participant with no ADA positive sample after the initiation of treatment.
Time frame: From first dose to 100 days after last dose (up to approximately 126 weeks)
Population: All participants who receive at least 1 dose of drug and have at least 1 ADA sample available. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Liri | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Nivo | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Liri | 3 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Nivo | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Nivo | 4 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Liri | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Nivo | 14 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Nivo | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Liri | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Liri | 10 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Liri | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Nivo | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Nivo | 13 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Liri | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Nivo | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Nivo | 3 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Liri | 10 Participants |
| Part 1/2: Liri 1 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Liri | 0 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Liri | 21 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Liri | 20 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Liri | 234 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Nivo | 14 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Nivo | 43 Participants |
| Part 1/2: Liri 3 + Nivo 3 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Nivo | 212 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Nivo | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Liri | 4 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Liri | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Nivo | 3 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | Baseline ADA Positive - Ipi | 1 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Ipi | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Negative - Ipi | 3 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Liri | 0 Participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 | ADA Positive - Nivo | 0 Participants |
Secondary
Number of Participants With Clinical Laboratory Test Abnormalities - Part 3
Number of participants that experienced a clinical laboratory test abnormality, including hematology and serum chemistry, and thyroid panel abnormalities. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Laboratory tests are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 3 is severe, and Grade 4 is life threatening. Baseline is defined as the last non-missing measurement prior to the first dosing date and time.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants with available laboratory test measurements. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alanine Amino Transferase (ALT) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Leukocytes - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Leukocytes - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lipase, Total (Colorimetric Assay) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lipase, Total (Colorimetric Assay) - Grade 4 | 1 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Absolute Neutrophil Count - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Magnesium, Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Neutrophils (Absolute) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Neutrophils (Absolute) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Phosphorus, Inorganic - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Absolute Neutrophil Count - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Hemoglobin - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Albumin - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Albumin - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alkaline Phosphatase (ALP) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Amylase, Total - Grade 3 | 1 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Amylase, Total - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Aspartate Aminotransferase (AST) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Aspartate Aminotransferase (AST) - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Bilirubin, Total - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Ionized - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Ionized - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Total - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Total - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Creatinine - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Creatinine - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | G-Glutamyl Transferase (GGT) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Glucose, Fasting Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Glucose, Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Glucose, Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Hemoglobin - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Platelet Count - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lymphocytes (Absolute) - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lymphocytes (Absolute) - Grade 4 | 1 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Magnesium, Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Platelet Count - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Potassium, Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Potassium, Serum - Grade 4 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Sodium Serum - Grade 3 | 0 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Sodium Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Sodium Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Hemoglobin - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Bilirubin, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Leukocytes - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Corrected - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Leukocytes - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Corrected - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lipase, Total (Colorimetric Assay) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Hemoglobin - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lipase, Total (Colorimetric Assay) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Magnesium, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Platelet Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Phosphorus, Inorganic - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Magnesium, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Neutrophils (Absolute) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Sodium Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Neutrophils (Absolute) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Calcium, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Absolute Neutrophil Count - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Phosphorus, Inorganic - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Absolute Neutrophil Count - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Creatinine - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alanine Amino Transferase (ALT) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Platelet Count - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alanine Amino Transferase (ALT) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Creatinine - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Albumin - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lymphocytes (Absolute) - Grade 3 | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Albumin - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | G-Glutamyl Transferase (GGT) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alkaline Phosphatase (ALP) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Potassium, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Alkaline Phosphatase (ALP) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Glucose, Fasting Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Amylase, Total - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Lymphocytes (Absolute) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Amylase, Total - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Glucose, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Aspartate Aminotransferase (AST) - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Potassium, Serum - Grade 3 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Aspartate Aminotransferase (AST) - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Glucose, Serum - Grade 4 | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 | Bilirubin, Total - Grade 3 | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) - Part 3
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Number of Participants With Serious Adverse Events (SAEs) - Part 3 | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Number of Participants With Serious Adverse Events (SAEs) - Part 3 | 3 Participants |
Secondary
Overall Survival (OS) - Part 3
Overall Survival (OS) is defined as the time from date of first dose of study medication to the date of death for any cause. A participant who has not died will be censored at last known date alive. OS for a participant who initiated new cancer treatment, will also be censored at the date of the new treatment initiation. Estimated by Kaplan-Meier Method.
Time frame: From date of first dose of study medication to the date of death for any cause. (Up to approximately 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Overall Survival (OS) - Part 3 | NA Years |
| Part 1/2: Liri 0.3 + Nivo 3 | Overall Survival (OS) - Part 3 | 0.3 Years |
Secondary
Progression Free Survival (PFS) - Part 3
PFS is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Participants who died without a reported prior progression was considered to have progressed on the date of their death. Participants alive with no progression were censored on the last evaluable tumor assessment date. Participants who started subsequent therapy with no prior progression were censored at the last evaluable tumor assessment prior to initiation of the subsequent therapy. Participants with no post-baseline tumor assessment and alive were censored on the date of first dose. Progression is defined as At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Clinical deterioration in the absence of radiographic evidence is not considered progression.
Time frame: From first dose to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. (Up to approximately 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Progression Free Survival (PFS) - Part 3 | NA Months |
| Part 1/2: Liri 0.3 + Nivo 3 | Progression Free Survival (PFS) - Part 3 | 1.6 Months |
Secondary
Progression Free Survival Rate (PFSR) at 6 Months - Part 3
Percentage of treated participants remaining progression free and surviving at 6 months. For those participants who remain alive and have not progressed, PFS will be censored on the date of the last tumor assessment. Progression is defined as At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Clinical deterioration in the absence of radiographic evidence is not considered progression.
Time frame: At 6 months after first dose
Population: All treated participants in Part 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Progression Free Survival Rate (PFSR) at 6 Months - Part 3 | 50.0 Percentage of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | Progression Free Survival Rate (PFSR) at 6 Months - Part 3 | 33.3 Percentage of participants |
Secondary
The Number of Participant Deaths in the Study - Part 3
The number of participants who died.
Time frame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Part 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participant Deaths in the Study - Part 3 | 1 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participant Deaths in the Study - Part 3 | 3 Participants |
Secondary
The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5
Depth of response is defined as the target tumor burden percent change from baseline at nadir for each participant as measured by the number of participants with \>= 50% and \>= 80% tumor reduction. Tumor assessments are performed every 8 weeks from first dose date for 48 weeks, and then every 12 weeks thereafter until progressive disease (PD) or treatment discontinuation, whichever occurs earlier.
Time frame: From first dose until progressive disease (PD) or treatment discontinuation, whichever occurs earlier. (Up to approximately 2.5 years)
Population: All treated participants. Pre-specified for data to be collected only in Parts 3 and 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | WITH >=50% TUMOR REDUCTION | 1 Participants |
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | WITH >=80% TUMOR REDUCTION | 0 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | WITH >=50% TUMOR REDUCTION | 2 Participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | WITH >=80% TUMOR REDUCTION | 1 Participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | WITH >=50% TUMOR REDUCTION | 0 Participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 | WITH >=80% TUMOR REDUCTION | 0 Participants |
Secondary
The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5
The number of participants with 1% or 5% PD-L1 expression in the tumor cell membrane. Participants are considered positive if they show \>=1% or \>= 5% PD-L1 expression in the tumor cell membrane and negative if they show \< 1% or \< 5%. PD-L1 expression is defined as the percent of tumor cells demonstrating plasma membrane PDL1 staining of any intensity. PD-L1 will be evaluated by immunohistochemistry (IHC). PD-L1 status at pretreatment is considered positive if any pretreatment sample is positive. PDL1= programmed cell death ligand 1
Time frame: Pre-dose Day 1 (Cycles 1 ,3 ,5, 7, 9), Pre-dose Day 29 (Cycle 1, 2)
Population: All treated participants with available archival tumor sample and with pre- and on-treatment biopsies. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - positive | 2 Number of participants |
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - negative | 1 Number of participants |
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - negative | 1 Number of participants |
| Part 1/2 Liri 0.1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - positive | 2 Number of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - positive | 5 Number of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - negative | 7 Number of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - negative | 6 Number of participants |
| Part 1/2: Liri 0.3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - positive | 4 Number of participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - positive | 9 Number of participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - negative | 9 Number of participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - negative | 4 Number of participants |
| Part 1/2: Liri 1 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - positive | 4 Number of participants |
| Part 1/2: Liri 3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - negative | 104 Number of participants |
| Part 1/2: Liri 3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - positive | 127 Number of participants |
| Part 1/2: Liri 3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - positive | 77 Number of participants |
| Part 1/2: Liri 3 + Nivo 3 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - negative | 154 Number of participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - positive | 1 Number of participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 1 percent - negative | 0 Number of participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - negative | 1 Number of participants |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 | PD-L1 5 percent - positive | 0 Number of participants |
Secondary
Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 1 | 1.13 hour |
| Part 1/2 Liri 0.1 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 2 | 1.08 hour |
| Part 1/2: Liri 0.3 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 1 | 1.05 hour |
| Part 1/2: Liri 0.3 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 2 | 1.02 hour |
| Part 1/2: Liri 1 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 1 | 1.07 hour |
| Part 1/2: Liri 1 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 2 | 1.13 hour |
| Part 1/2: Liri 3 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 2 | 1.18 hour |
| Part 1/2: Liri 3 + Nivo 3 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 1 | 1.22 hour |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 1 | 1.03 hour |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 | Cycle 2 | 1.33 hour |
Secondary
Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5
Pharmacokinetics of lirilumab were derived from serum concentration versus time data. Geometric CV data is not available, therefore the Arithmetic %CV is represented in the table below.
Time frame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
Population: All treated participants who received at least 1 dose of lirilumab and have available serum concentration data. Pre-specified for data to be collected only in Parts 1, 2, and 5.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1/2 Liri 0.1 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 1 | 87.62 ng/mL |
| Part 1/2 Liri 0.1 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 2 | 358.55 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 2 | 1180.39 ng/mL |
| Part 1/2: Liri 0.3 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 1 | 521.28 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 2 | 4827.27 ng/mL |
| Part 1/2: Liri 1 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 1 | 2572.90 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 2 | 11392.89 ng/mL |
| Part 1/2: Liri 3 + Nivo 3 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 1 | 6195.04 ng/mL |
| Part 5: Liri 3 + Nivo 3 + Ipi 1 | Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 | Cycle 1 | 5190.00 ng/mL |