A Study of an Anti-KIR Antibody Lirilumab in Combination With an Anti-PD1 Antibody Nivolumab and Nivolumab Plus an Anti-CTLA-4 Ipilimumab Antibody in Patients With Advanced Solid Tumors

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.

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 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 participants who died.

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) 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.

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.

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.

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.

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) 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.

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.

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.

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.

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 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 participants who died.

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 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 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

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.

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.

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.

Pharmacokinetics of lirilumab were derived from serum concentration versus time data.

Pharmacokinetics of lirilumab were derived from serum concentration versus time data.

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.

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.

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.

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.

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.

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.

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.

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.