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

• ClinicalTrials.gov Identifier: NCT01953692
• Recruitment Status: Completed
• First Posted: October 1, 2013
• Results First Posted: July 12, 2021
• Last Update Posted: August 4, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Myelodysplastic Syndrome; Multiple Myeloma; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Primary Mediastinal B-Cell Lymphoma	Biological: Pembrolizumab; Drug: Lenalidomide 20 mg; Drug: Lenalidomide 25 mg	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 197 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib Multi-Cohort Trial of MK-3475 (Pembrolizumab) in Subjects With Hematologic Malignancies
• Actual Study Start Date: November 22, 2013
• Actual Primary Completion Date: June 26, 2020
• Actual Study Completion Date: June 26, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: Myelodysplastic Syndrome (MDS); Participants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: 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 OR 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: Cohort 3: Relapsed/Refractory (R/R) Hodgkin lymphoma (HL); Participants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL); 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas; Participants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: Cohort 4C: R/R Follicular Lymphoma (FL); Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL); Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 20 mg; 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Lenalidomide 20 mg; oral capsule; Other Name: REVLIMID®
Experimental: Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 25 mg; 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Lenalidomide 25 mg; oral capsule; Other Name: REVLIMID®

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Experienced One or More Adverse Events (AEs): [ Time Frame: Up to approximately 78.5 months ]
   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.
2. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 78.5 months ]
   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.
3. Objective Response Rate (ORR) in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
   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.
4. Objective Response Rate (ORR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) [ Time Frame: Up to approximately 78.5 months ]
   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.
5. Complete Remission Rate (CRR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
   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.
6. Objective Response Rate (ORR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) [ Time Frame: Up to approximately 78.5 months ]
   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.
7. Objective Response Rate (ORR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) [ Time Frame: Up to approximately 78.5 months ]
   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.
8. 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) [ Time Frame: Up to approximately 78.5 months ]
   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.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
   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.
2. Overall Survival (OS) [ Time Frame: Up to approximately 78.5 months ]
   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.
3. Overall Survival (OS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) [ Time Frame: Up to approximately 78.5 months ]
   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.
4. 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) [ Time Frame: Up to approximately 78.5 months ]
   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.
5. Duration of Response (DOR) in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
   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.
6. Duration of Response (DOR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) [ Time Frame: Up to approximately 78.5 months ]
   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.
7. Duration of Response (DOR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
   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.
8. Duration of Response (DOR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) [ Time Frame: Up to approximately 78.5 months ]
   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.
9. Duration of Response (DOR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) [ Time Frame: Up to approximately 78.5 months ]
   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.
10. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
11. Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
12. Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
13. Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
14. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
15. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
16. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
17. Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
    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.
18. Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
    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.
19. Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
    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.
20. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
21. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
22. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
23. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
24. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
25. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
26. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
27. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
28. 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) [ Time Frame: Up to approximately 78.5 months ]
    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.
29. Progression-free Survival (PFS) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) [ Time Frame: Up to approximately 78.5 months ]
    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.
30. Progression-free Survival (PFS) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) [ Time Frame: Up to approximately 78.5 months ]
    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.
31. Progression-free Survival (PFS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) [ Time Frame: Up to approximately 78.5 months ]
    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.
32. Progression-free Survival (PFS) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) [ Time Frame: Up to approximately 78.5 months ]
    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.
33. Progression-free Survival (PFS) in Participants Pooled From the Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) [ Time Frame: Up to approximately 78.5 months ]
    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.
34. Marrow Complete Response (mCR) in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
35. Cytogenic Complete Response in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
36. Cytogenic Partial Response in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
37. Erythroid Response in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
38. Neutrophil Response in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
39. Platelet Response in Cohort 1: Myelodysplastic Syndrome (MDS) [ Time Frame: Up to approximately 78.5 months ]
    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.
40. Time to Progression (TTP) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) [ Time Frame: Up to approximately 78.5 months ]
    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.
41. Stringent Complete Remission (sCR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) [ Time Frame: Up to approximately 78.5 months ]
    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.
42. Complete Response (CR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) [ Time Frame: Up to approximately 78.5 months ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Has confirmed diagnosis of relapse or refractory Multiple Myeloma (enrollment completed), Primary mediastinal Large B cell Lymphoma, non-Hodgkin lymphoma (NHL), Follicular Lymphoma, Diffuse Large B cell lymphoma (enrollment discontinued), Hodgkin lymphoma or Myelodysplastic syndrome (enrollment completed).
• Has measurable disease
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Demonstrates adequate organ function
• Prior therapy criteria must be met
• Female participants of childbearing potential and male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy

Exclusion Criteria:

• Is currently participating in and receiving study therapy or has participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of study therapy
• Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years, has received a live vaccine within 30 days of planned start of study therapy, has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1, received a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered from adverse events due to a previously administered agent
• Has known clinically active central nervous system (CNS) involvement
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has evidence of interstitial lung disease, active non-infectious pneumonitis, a known additional malignancy that is progressing or requires active treatment, an active infection requiring intravenous systemic therapy, an active autoimmune disease that has required systemic therapy, a known Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C (HCV) infection
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study starting with the pre-screening or screening visit through 120 days after the last dose of study therapy
• Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Has known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] April 16, 2020

More Information

Additional Information:

Merck Oncology Clinical Trials Information 

Publications of Results:

Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016 Nov 1;34(31):3733-3739. doi: 10.1200/JCO.2016.67.3467.

Ribrag V, Avigan DE, Green DJ, Wise-Draper T, Posada JG, Vij R, Zhu Y, Farooqui MZH, Marinello P, Siegel DS. Phase 1b trial of pembrolizumab monotherapy for relapsed/refractory multiple myeloma: KEYNOTE-013. Br J Haematol. 2019 Aug;186(3):e41-e44. doi: 10.1111/bjh.15888. Epub 2019 Apr 1. No abstract available.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Garcia-Manero G, Ribrag V, Zhang Y, Farooqui M, Marinello P, Smith BD. Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Leuk Lymphoma. 2022 Jul;63(7):1660-1668. doi: 10.1080/10428194.2022.2034155. Epub 2022 Mar 4.

Griffin GK, Weirather JL, Roemer MGM, Lipschitz M, Kelley A, Chen PH, Gusenleitner D, Jeter E, Pak C, Gjini E, Chapuy B, Rosenthal MH, Xu J, Chen BJ, Sohani AR, Lovitch SB, Abramson JS, Ishizuka JJ, Kim AI, Jacobson CA, LaCasce AS, Fletcher CD, Neuberg D, Freeman GJ, Hodi FS, Wright K, Ligon AH, Jacobsen ED, Armand P, Shipp MA, Rodig SJ. Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma. Blood. 2021 Mar 11;137(10):1353-1364. doi: 10.1182/blood.2020006464.

Armand P, Kuruvilla J, Michot JM, Ribrag V, Zinzani PL, Zhu Y, Marinello P, Nahar A, Moskowitz CH. KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. Blood Adv. 2020 Jun 23;4(12):2617-2622. doi: 10.1182/bloodadvances.2019001367.

Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Ozcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. doi: 10.1200/JCO.19.01389. Epub 2019 Oct 14.

van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.

Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, Zhang Y, Chlosta S, Shipp MA, Armand P. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017 Jul 20;130(3):267-270. doi: 10.1182/blood-2016-12-758383. Epub 2017 May 10.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01953692
• Other Study ID Numbers: 3475-013; 2013-001603-37 ( EudraCT Number ); MK-3475-013 ( Other Identifier: Merck )
• First Posted: October 1, 2013
• Results First Posted: July 12, 2021
• Last Update Posted: August 4, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme LLC:

PD1; PD-1; PDL1; PD-L1

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Myelodysplastic Syndromes; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoma, Non-Hodgkin; Bone Marrow Diseases; Pembrolizumab; Lenalidomide; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors