Clinical Trials /

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

NCT01953692

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Mediastinal Large B-Cell Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Pembrolizumab (MK-3475) in Participants With Blood Cancers (MK-3475-013/KEYNOTE-013)
  • Official Title: A Phase Ib Multi-Cohort Trial of MK-3475 (Pembrolizumab) in Subjects With Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 3475-013
  • SECONDARY ID: 2013-001603-37
  • SECONDARY ID: MK-3475-013
  • NCT ID: NCT01953692

Conditions

  • Myelodysplastic Syndrome
  • Multiple Myeloma
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Primary Mediastinal B-Cell Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KEYTRUDA®Cohort 1: Myelodysplastic Syndrome (MDS)
Lenalidomide 20 mgREVLIMID®Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 20 mg
Lenalidomide 25 mgREVLIMID®Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 25 mg

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Myelodysplastic Syndrome (MDS)ExperimentalParticipants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.
  • Pembrolizumab
Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)ExperimentalParticipants 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.
  • Pembrolizumab
Cohort 3: Relapsed/Refractory (R/R) Hodgkin lymphoma (HL)ExperimentalParticipants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.
  • Pembrolizumab
Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL)ExperimentalParticipants 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.
  • Pembrolizumab
Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell LymphomasExperimentalParticipants received pembrolizumab 10 mg/kg by intravenous (IV) infusion on Day 1 of each 14-day cycle.
  • Pembrolizumab
Cohort 4C: R/R Follicular Lymphoma (FL)ExperimentalParticipants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.
  • Pembrolizumab
Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL)ExperimentalParticipants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.
  • Pembrolizumab
Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 20 mgExperimentalParticipants 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.
  • Pembrolizumab
  • Lenalidomide 20 mg
Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 25 mgExperimentalParticipants 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.
  • Pembrolizumab
  • Lenalidomide 25 mg

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Who Experienced One or More Adverse Events (AEs):
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Progression-free Survival (PFS) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Progression-free Survival (PFS) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Marrow Complete Response (mCR) in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Cytogenic Complete Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Cytogenic Partial Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Erythroid Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Neutrophil Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Platelet Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Time to Progression (TTP) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Stringent Complete Remission (sCR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.
Measure:Complete Response (CR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
Time Frame:Up to approximately 78.5 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • PD1
  • PD-1
  • PDL1
  • PD-L1

Last Updated

August 4, 2021