A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Participants With Hematologic Malignancies

ORR is percentage of participants achieving a complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR) or PR. IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils \>1.5\*10\^9/L, platelets \>100\*10\^9/L, Hgb \>11 g/dL and absolute lymphocyte count \<4000/mcL; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR- \>=50% drop in lymphocyte count from baseline or \<=4.0\*10\^9/L with following: \>=50% decrease in sum products of up to 6 lymph nodes, no new enlarged lymph nodes, When abnormal, \>=50% decrease in enlargement of spleen from baseline or normalization and a response in 1 of following: Neutrophils \>1.5\*10\^9/L, Platelets\>100000/mcL and Hgb\>11 g/dL or \>=50% improvement over baseline in all. This outcome measure was planned to be analyzed for specified arm only.

Time frame: Up to 6 years 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab). The ORR evaluation criteria were disease specific and hence the analysis was done as per disease cohorts for this outcome measure as pre-planned.

ORR defined as percentage of participants achieving a CR, CRi, nPR or PR. As per Non-Hodgkin Lymphoma, Cheson 2014, CR is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is \>= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive disease (PD) \>= 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. This outcome measure was planned to be analyzed for specified arms only.

Time frame: Up to 6 years 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab). The ORR evaluation criteria were disease specific and hence the analysis was done as per disease cohorts for this outcome measure as pre-planned.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs for the treatment phase included events with an onset date/time on or after the start of study intervention through end of study were considered as treatment-emergent.

Time frame: Up to 6 years 10 months

Population: The safety population included all participants who received at least 1 dose of study drugs (either ibrutinib or nivolumab).

DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and date of first documented evidence of progressive disease or death or date of censoring. iWCLL 2008 criteria for progressive disease: New enlarged nodes \>1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; \>= 50% increase from nadir in existing lymph node or \>=50% increase from nadir in sum of product of diameters of multiple nodes; \>=50% increase from nadir in enlargement of liver or spleen; \>=50% increase from baseline in lymphocyte count (\>=5\*10\^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.

Time frame: Up to 6 years 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and achieved either PR or better (including PRL only for CLL participants).

Duration of stable disease or better was defined as duration from the start of the treatment until the criteria for progression were met. IWCLL 2008 criteria for progressive disease: New enlarged nodes \>1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; \>= 50% increase from nadir in existing lymph node or \>=50% increase from nadir in sum of product of diameters of multiple nodes; \>=50% increase from nadir in enlargement of liver or spleen; \>=50% increase from baseline in lymphocyte count (and to \>=5\*10\^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.

Time frame: Up to 6 years and 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and met criteria for progressive disease. Here 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.

OS was defined as duration from the date of first dose of study drug to the date of the participant's death.

Time frame: Up to 6 years 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and were responders.

Percentage of participants with lymphoma-related symptoms were reported. These symptoms included B-symptoms, recurrent fever, night sweats, weight loss, other disease-related symptoms, itching, fatigue, physical discomfort and any other.

Time frame: Up to 6 years 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab).

PFS is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. Participants who were progression-free and alive or had unknown status were censored at the last tumor assessment. IWCLL 2008 criteria for progressive disease: New enlarged nodes \>1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; \>= 50% increase from nadir in existing lymph node or \>=50% increase from nadir in sum of product of diameters of multiple nodes; \>=50% increase from nadir in enlargement of liver or spleen; \>=50% increase from baseline in lymphocyte count (and to \>=5\*10\^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.

Time frame: Up to 6 years 11 months

Population: The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and met criteria for progressive disease.