Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Lymphoma

Hematologic Neoplasms

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoma, Non-Hodgkin

Bone Marrow Diseases

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenalidomide

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Participants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle OR 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.

Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.

Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle + lenalidomide 20 mg orally (PO) every day (QD) for 21 consecutive days with 7 days off within 28-day cycles.

Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle + lenalidomide 25 mg PO QD for 21 consecutive days with 7 days off within 28-day cycles.

Lenalidomide 20 mg

Lenalidomide 25 mg

Medical Director

The purpose of this trial is to evaluate the safety, tolerability, and efficacy of pembrolizumab (MK-3475, KEYTRUDA®) and pembrolizumab in combination with lenalidomide (Cohort 5 only) in hematologic malignancies. The primary study hypotheses are that treatment with pembrolizumab will result in a clinically meaningful improvement in Objective Response Rate (ORR) or Complete Remission Rate (CRR).

The study includes an initial dose determination to establish the recommended phase 2 dose (RP2D) of lenalidomide given in combination with pembrolizumab in Cohort 5.

With Protocol Amendment 08, enrollment in the Multiple Myeloma arm (Cohort 2) has been completed and no further enrollment will be allowed and enrollment in the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma arm (Cohort 5) has been discontinued and no further enrollment will be allowed.

A Trial of Pembrolizumab (MK-3475) in Participants With Blood Cancers (MK-3475-013/KEYNOTE-013)

A Phase Ib Multi-Cohort Trial of MK-3475 (Pembrolizumab) in Subjects With Hematologic Malignancies

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. CR was demonstrated by ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow (persistent dysplasia will be noted) and normal findings for hemoglobin, platelet count, neutrophil count, and absence of blasts in the blood. PR was all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pre-treatment but still \>5%. Cellularity and morphology are not relevant. Cohort 1 was evaluated statistically by comparing the ORR for pembrolizumab to a fixed efficacy target of 10% using a binomial exact test. The percentage of participants with CR and PR as assessed by the investigator is presented.

ORR was defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR=negative immunofixation of serum and urine+disappearance of soft tissue plasmacytomas+≤5% plasma cells in the bone marrow (BM); sCR=stringent complete response, CR as above+normal serum free light-chain ratio and absence of clonal cells in BM; VGPR=serum+urine M-protein (M-p) by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-p+urine M-p \<100 mg/24 hr; PR=≥50% reduction of serum M-p+reduction in 24-hour urine M-p by ≥90% or to \<200 mg/24 hours. Cohort 2 was evaluated statistically by comparing the ORR for pembrolizumab to a fixed efficacy target of 25% using a binomial exact test. The percentage of participants with CR, sCR, PR, VGPR as assessed by the investigator is presented.

CRR was defined as the percentage of participants with complete remission according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. Complete remission was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. Cohort 3 was evaluated statistically by comparing the complete remission for pembrolizumab to a fixed efficacy target of 10% using a binomial exact test. The percentage of participants with complete remission as assessed by the investigator is presented.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. The pooled Cohort 4 sub-cohorts were evaluated statistically by comparing the ORR for pembrolizumab to a fixed efficacy target of 25% using a binomial exact test. The percentage of participants with CR and PR as assessed by the investigator is presented.

ORR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. Per protocol, Cohorts 4A, 4B, 4C, and 4D were not planned to be compared to an efficacy target. The percentage of participants with CR and PR as assessed by the investigator is presented.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. Per protocol, pooled Cohort 5 was not planned to be evaluated statistically compared to a fixed efficacy target. The percentage of participants with CR and PR as assessed by the investigator is presented.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. The percentage of participants who experience ORR as assessed by the investigator is presented.

OS was defined as the time from first dose of study treatment to death due to any cause. OS was calculated from product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.

For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. CR was demonstrated by ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow (persistent dysplasia will be noted) and normal findings for hemoglobin, platelet count, neutrophil count, and absence of blasts in the blood. PR was all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pre-treatment but still \>5%. Cellularity and morphology are not relevant. DOR as assessed by the investigator is presented.

For participants who demonstrated a confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), DOR was defined as the time from sCR, CR, VGPR, or PR to documented disease progression or death. Response was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR=negative immunofixation of serum and urine+disappearance of soft tissue plasmacytomas+≤5% plasma cells in the bone marrow (BM); sCR=stringent complete response, CR as above+normal serum free light-chain ratio and absence of clonal cells in BM; VGPR=serum+urine M-protein (M-p) by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-p+urine M-p \<100 mg/24 hr; PR=≥50% reduction of serum M-p+reduction in 24-hour urine M-p by ≥90% or to \<200 mg/24 hours. DOR as assessed by the investigator is presented.

For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. DOR as assessed by the investigator is presented.

DOR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. DOR as assessed by the investigator is presented.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. CR was demonstrated by ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow (persistent dysplasia will be noted) and normal findings for hemoglobin, platelet count, neutrophil count, and absence of blasts in the blood. PR was all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pre-treatment but still \>5%. Cellularity and morphology are not relevant. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. CR was demonstrated by ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow (persistent dysplasia will be noted) and normal findings for hemoglobin, platelet count, neutrophil count, and absence of blasts in the blood. PR was all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pre-treatment but still \>5%. Cellularity and morphology are not relevant. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of \<1%) participants.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. CR was demonstrated by ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow (persistent dysplasia will be noted) and normal findings for hemoglobin, platelet count, neutrophil count, and absence of blasts in the blood. PR was all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pre-treatment but still \>5%. Cellularity and morphology are not relevant. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status.

ORR was defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR=negative immunofixation of serum and urine+disappearance of soft tissue plasmacytomas+≤5% plasma cells in the bone marrow (BM); sCR=stringent complete response, CR as above+normal serum free light-chain ratio and absence of clonal cells in BM; VGPR=serum+urine M-protein (M-p) by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-p+urine M-p \<100 mg/24 hr; PR=≥50% reduction of serum M-p+reduction in 24-hour urine M-p by ≥90% or to \<200 mg/24 hours. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR, sCR, PR, VGPR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants.

ORR was defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR=negative immunofixation of serum and urine+disappearance of soft tissue plasmacytomas+≤5% plasma cells in the bone marrow (BM); sCR=stringent complete response, CR as above+normal serum free light-chain ratio and absence of clonal cells in BM; VGPR=serum+urine M-protein (M-p) by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-p+urine M-p \<100 mg/24 hr; PR=≥50% reduction of serum M-p+reduction in 24-hour urine M-p by ≥90% or to \<200 mg/24 hours. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR, sCR, PR, VGPR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of \<1%) participants.

ORR was defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR=negative immunofixation of serum and urine+disappearance of soft tissue plasmacytomas+≤5% plasma cells in the bone marrow (BM); sCR=stringent complete response, CR as above+normal serum free light-chain ratio and absence of clonal cells in BM; VGPR=serum+urine M-protein (M-p) by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-p+urine M-p \<100 mg/24 hr; PR=≥50% reduction of serum M-p+reduction in 24-hour urine M-p by ≥90% or to \<200 mg/24 hours. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR, sCR, PR, VGPR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of \<1%) participants.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status.

ORR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants.

ORR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of \<1%) participants.

ORR was evaluated for each of Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in bone marrow, spleen, liver, and lymph nodes. PR was \>50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and \>50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and for nodal masses. PR was \>50% decrease in the sum of product diameters for ≤6 target dominant masses for lymph nodes, spleen nodules, and liver nodules and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and for nodal masses. PR was \>50% decrease in the sum of product diameters for ≤6 target dominant masses for lymph nodes, spleen nodules, and liver nodules and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of \<1%) participants.

ORR was defined as the percentage of participants with response (complete response \[CR\] or partial response \[PR\]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and for nodal masses. PR was \>50% decrease in the sum of product diameters for ≤6 target dominant masses for lymph nodes, spleen nodules, and liver nodules and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status.

PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. PD was defined as ≥1 of the following: increase of ≥25% from baseline of serum or urine M-component or \>10 mg/dl difference between involved and uninvolved free light chain levels; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; or hypercalcemia. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented.

PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. PD was the appearance of any new lesion, \>50% increase in the sum of product diameters (SPD) of ≥1 lymph node, or a \>50% increase in the longest diameter of a previous lymph node, lesions positron emission tomography (PET) positive if 18F-fluorodeoxyglucose (FDG)-avid lymphoma or PET positive prior to therapy for lymph nodes; \>50% increase from nadir in the SPD of previous lesions in the liver and spleen; or new or recurrent involvement of the bone marrow. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented.

mCR was defined as ≤5% myeloblasts in the bone marrow with a decrease in myeloblasts ≥50% over pretreatment according to the modified International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. The percentage of participants with mCR as assessed by the investigator is presented.

Cytogenic complete response was evaluated by detection of chromosomal abnormalities by cytogenic techniques and assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Cytogenic complete response was defined as the disappearance of the chromosomal abnormality detected pre-treatment without the appearance of new chromosomal abnormalities. The percentage of participants with cytogenic complete response as assessed by the investigator is presented.

Cytogenic partial response was evaluated by detection of chromosomal abnormalities by cytogenic techniques and assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Cytogenic partial response was defined as ≥50% reduction of the chromosomal abnormality detected pre-treatment. The percentage of participants with cytogenic partial response as assessed by the investigator is presented.

Erythroid response was measured as an evaluation of hematologic improvement and was assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Erythroid response baseline was based on an average of at least 2 pre-treatment measurements taken ≥1 week apart and not influenced by transfusions. Responses were considered significant if they lasted for ≥8 weeks. Criteria for an erythroid response include: hemoglobin (Hgb) increase by ≥1.5 grams/deciliter (g/dl) from pretreatment or reduction of ≥4 transfusions/8 weeks compared with the pre-treatment transfusion number in the previous 8 weeks. Only transfusions given for a Hgb of ≤9.0 g/dl pretreatment counted for response evaluation. The percentage of participants with an erythroid response as assessed by the investigator is presented.

Neutrophil response was measured as an evaluation of hematologic improvement and was assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Neutrophil response baseline was based on an average of at least 2 pre-treatment measurements taken ≥1 week apart and not influenced by transfusions. Responses were considered significant if they lasted for ≥8 weeks. Criterion for a neutrophil response was a ≥100% increase in neutrophil count from pre-treatment and an absolute increase of \>0.5 x 10\^9/Liter. The percentage of participants with a neutrophil response as assessed by the investigator is presented.

Platelet response was measured as an evaluation of hematologic improvement and was assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Platelet response baseline was based on an average of at least 2 pre-treatment measurements taken ≥1 week apart and not influenced by transfusions. Responses were considered significant if they lasted for ≥8 weeks. Criterion for a platelet response was an absolute increase of ≥30 x 10\^9/Liter platelet count for participants with a pre-treatment count of ≥20 x 10\^9/Liter and for participants with a pre-treatment count of \<20 x 10\^9/Liter there must have been an absolute increase to ≥20 x 10\^9/Liter and a ≥100% increase in pre-treatment level. The percentage of participants with a platelet response as assessed by the investigator is presented.

TTP was defined as the time from first dose of study treatment to disease progression. Progressive disease was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. PD was defined as ≥1 of the following: increase of ≥25% from baseline of serum or urine M-component or \>10 mg/dl difference between involved and uninvolved free light chain levels; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; bone marrow plasma cell percentage absolute % must be ≥10%; or hypercalcemia. The TTP as assessed by the investigator is presented.

sCR was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. sCR was defined as complete response \[CR\] plus normal serum free light-chain ratio and absence of clonal cells in bone marrow. CR criteria are negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and ≤5% plasma cells in the bone marrow. The percentage of participants with sCR as assessed by the investigator is presented.

CR was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR was defined as negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and \<5% plasmacytomas in the bone marrow. The percentage of participants with CR as assessed by the investigator is presented.

Merck Sharp & Dohme LLC

The analysis population for adverse events (AEs) consisted of all participants who received ≥1 dose of study treatment. Per protocol, disease progression was not considered an AE unless considered related to study treatment. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "neoplasm progression", "malignant neoplasm progression" and "disease progression" not related to study treatment are excluded.

Participants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle

Cohort 1: Myelodysplastic Syndrome (MDS)

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle OR 10 mg/kg by IV infusion on Day 1 of each 14-day cycle.

Cohort 2: Relapsed Refractory or Refractory(rR/R) Multiple Myeloma (MM)

Participants received pembrolizumab 10 mg/kg by IV infusion on Day 1 of each 14-day cycle.

Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL)

Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle.

Cohort 4C: R/R Follicular Lymphoma (FL)

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle

Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL)

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle + lenalidomide 20 mg orally (PO) every day (QD) for 21 consecutive days with 7 days off within 28-day cycles. The 20 mg dose of lenalidomide is the RP2D.

Cohort 5: R/R DLBCL Pembrolizumab+Lenalidomide 20 mg (RP2D)

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle + lenalidomide 25 mg PO QD for 21 consecutive days with 7 days off within 28-day cycles. The 25 mg dose of lenalidomide was the starting dose for dose determination.

Cohort 5: R/R DLBCL Pembrolizumab+Lenalidomide 25 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

All participants who received at least one dose of study treatment.

Enrollment of participants into Cohort 5 of this study was discontinued after the Food and Drug Administration (FDA) implemented a clinical hold after determining the risks of pembrolizumab + lenalidomide outweighed any potential benefit.

Senior Vice President, Global Clinical Development

Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)

Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle + lenalidomide 25 mg PO QD for 21 consecutive days with 7 days off within 28-day cycles.

All participants who received at least 1 dose of study treatment.

Number of Participants Who Experienced One or More Adverse Events (AEs):

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

Comparison to a fixed efficacy target of 10%. H0: p ≤ 0.10 versus H1: p \> 0.10

All participants in Cohort 1 with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Cohort 1: Myelodysplastic Syndrome (MDS)

Comparison to a fixed efficacy target of 25%. H0: p ≤ 0.25 versus H1: p \> 0.25

All participants in Cohort 2 with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)

All participants in Cohort 3 with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Complete Remission Rate (CRR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

Participants from the pooled Cohort 4 NHL sub-cohorts (Cohorts 4A+4B+4C+4D) received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle OR 10 mg/kg by IV infusion on Day 1 of each 14-day cycle.

Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D)

All participants pooled from the Cohort 4 NHL sub-cohorts (Cohorts 4A+4B+4C+4D) with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (NHL).

Objective Response Rate (ORR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)

All participants in Cohorts 4A, 4B, 4C, and 4D with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (NHL).

Objective Response Rate (ORR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)

Participants from the pooled Cohort 5 received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle + lenalidomide 20 mg or 25 mg PO QD for 21 consecutive days with 7 days off within 28-day cycles.

Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide)

All participants pooled from Cohort 5 (pembrolizumab + 20 or 25 mg doses of lenalidomide) with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (DLBCL) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.

Objective Response Rate (ORR) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Objective Response Rate (ORR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

All participants with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Overall Survival (OS)

Overall Survival (OS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)

All participants pooled from the Cohort 5 (pembrolizumab + 20 or 25 mg doses of lenalidomide) with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (DLBCL) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.

Overall Survival (OS) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

All participants in Cohort 1 with a baseline efficacy evaluation, at least 1 post-baseline efficacy evaluation, and who demonstrated a PR or CR. DOR was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 1.

Duration of Response (DOR) in Cohort 1: Myelodysplastic Syndrome (MDS)

All participants in Cohort 2 with a baseline efficacy evaluation, at least 1 post-baseline efficacy evaluation, and who demonstrated a VGPR, PR, sCR, or CR. DOR was not analyzed because there were no participants who demonstrated a VGPR, PR, sCR, or CR in Cohort 2.

Duration of Response (DOR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)

All participants in Cohort 3 with a baseline efficacy evaluation, at least 1 post-baseline efficacy evaluation, and who demonstrated a PR or CR.

Duration of Response (DOR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

All participants pooled from the Cohort 4 NHL sub-cohorts (Cohorts 4A+4B+4C+4D) with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation and who demonstrated a PR or CR. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (NHL).

Duration of Response (DOR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)

All participants in Cohorts 4A, 4B, 4C, and 4D with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation and who demonstrated a PR or CR.

Duration of Response (DOR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)

All participants pooled from the Cohort 5 (pembrolizumab + 20 or 25 mg doses of lenalidomide) with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation and who demonstrated a PR or CR. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (DLBCL) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.

Duration of Response (DOR) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

All participants in Cohort 1, who were PD-L1 positive, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR by PD-L1 status was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 1.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 1: Myelodysplastic Syndrome (MDS)

All participants in Cohort 1, who were PD-L1 negative, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR by PD-L1 status was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 1.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 1: Myelodysplastic Syndrome (MDS)

All participants in Cohort 1, who had an indeterminate PD-L1 status, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR by PD-L1 status was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 1.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 1: Myelodysplastic Syndrome (MDS)

All participants in Cohort 2, who were PD-L1 positive, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR by PD-L1 status was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 2.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)

All participants in Cohort 2, who were PD-L1 negative, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR by PD-L1 status was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 2.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)

All participants in Cohort 2, who had an indeterminate PD-L1 status, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR by PD-L1 status was not analyzed because there were no participants who demonstrated a PR or CR in Cohort 2.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)

All participants in Cohort 3, who were PD-L1 positive, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

All participants in Cohort 3, who were PD-L1 negative, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

All participants in Cohort 3, who had an indeterminate PD-L1 status, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)

All participants pooled from the Cohort 4 NHL sub-cohorts (Cohorts 4A+4B+4C+4D), who were PD-L1 positive, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (NHL).

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)

All participants pooled from the Cohort 4 NHL sub-cohorts (Cohorts 4A+4B+4C+4D), who were PD-L1 negative, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (NHL).

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)

All participants pooled from the Cohort 4 NHL sub-cohorts (Cohorts 4A+4B+4C+4D), who had an indeterminate PD-L1 status, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (NHL).

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)

All participants in Cohorts 4A, 4B, 4C, and 4D, who were PD-L1 positive, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)

All participants in Cohorts 4A, 4B, 4C, and 4D, who were PD-L1 negative, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)

All participants in Cohorts 4A, 4B, 4C, and 4D, who had an indeterminate PD-L1 status, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. ORR was not analyzed for Cohort 4B because there were no participants with a PD-L1 status of indeterminate in this Cohort.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)

All participants pooled from Cohort 5 (pembrolizumab + 20 or 25 mg doses of lenalidomide), who were PD-L1 positive, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (DLBCL) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

All participants pooled from Cohort 5 (pembrolizumab + 20 or 25 mg doses of lenalidomide), who were PD-L1 negative, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (DLBCL) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

All participants pooled from Cohort 5 (pembrolizumab + 20 or 25 mg doses of lenalidomide), who had an indeterminate PD-L1 status, with a baseline efficacy evaluation and at least 1 post-baseline efficacy evaluation. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (DLBCL) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.

Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Spots Global Cancer Trial Database for lenalidomide 25 mg