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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hodgkin Lymphoma; Primary Mediastinal B-Cell Lymphoma; Multiple Myeloma; Follicular Lymphoma; Diffuse Large B-Cell Lymphoma; Myelodysplastic Syndrome; Non-Hodgkin Lymphoma

Treatments: Biological: Pembrolizumab; Drug: Lenalidomide 20 mg; Drug: Lenalidomide 25 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01953692

3475-013

MK-3475-013 (Other Identifier)

2013-001603-37 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 197 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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197 participants in 9 patient groups

Cohort 1: Myelodysplastic Syndrome (MDS)

Experimental group

Description:

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

Treatment:

Biological: Pembrolizumab

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

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab

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

Experimental group

Description:

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

Treatment:

Biological: Pembrolizumab

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

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab

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

Experimental group

Description:

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

Treatment:

Biological: Pembrolizumab

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

Experimental group

Description:

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

Treatment:

Biological: Pembrolizumab

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

Experimental group

Description:

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

Treatment:

Biological: Pembrolizumab

Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 20 mg

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide 20 mg

Biological: Pembrolizumab

Cohort 5: R/R DLBCL pembrolizumab+lenalidomide 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide 25 mg

Biological: Pembrolizumab