Efficacy and Safety Study of Pembrolizumab (MK-3475) in Combination With Daratumumab in Participants With Relapsed Refractory Multiple Myeloma (MK-3475-668/KEYNOTE-668)

NCT03221634 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 3475-6682017-001001-32
• Study Type: interventional
• Target: N/A
• Locations: 6 countries
• Sites: 23

Brief Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with daratumumab in participants with relapsed refractory multiple myeloma (rrMM). The primary outcome measure for this study is the assessment of Objective Response Rate (ORR) in participants with rrMM.

Conditions

Multiple Myeloma

Keywords

Programmed cell death 1 receptor (PD1); PD-1; Programmed cell death ligand 1 receptor (PDL1); PD-L1

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants who experience a partial response (PR; ≥50% reduction of serum myeloma (M)-protein plus reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg per 24 hours) or better per International Myeloma Working Group (IMWG) 2016, based on investigator assessment.

  Up to approximately 2 years

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  Up to approximately 2 years

• Duration of Response (DOR)

  Up to approximately 2 years

• Adverse Events (AEs)

  Up to approximately 27 months

• Study Treatment Discontinuations Due to AEs

  Up to approximately 2 years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion once every 3 weeks (Q3W) for up to 35 administrations (up to approximately 2 years) and receive daratumumab 16 mg/kg by IV infusion on Days 1, 8, 15, and 22 of Cycles 1-2; on Days 1 and 15 of Cycles 3-6, and on Day 1 of Cycle 7 and beyond, for up to 2 years. Each cycle is 28 days long.

Biological: Pembrolizumab; Biological: Daratumumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475

Pembrolizumab

Daratumumab BIOLOGICAL

IV infusion

Also known as: DARZALEX®

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a confirmed diagnosis of active MM and measurable disease defined as: a.) Serum M-protein levels ≥0.5 g/dL or b.) Urine M-protein levels ≥200 mg/24 hours or c.) For participants without measurable serum and urine M-protein levels, an abnormal serum free light chain ratio (FLC κ/λ) with involved FLC level ≥100 mg/L.
• Has undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and must have failed their last line of treatment defined as lack of response or documented disease progression during or within 60 days of completing their last anti-myeloma therapy.
• Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD; i.e., lenalidomide, thalidomide, or pomalidomide) AND a proteasome inhibitor (PI; i.e., bortezomib, ixazomib, or carfilzomib) alone or in combination and participant must have failed therapy with an IMiD or PI or both.
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Has adequate organ function.
• Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants must not be pregnant, breastfeeding, and must agree to use (or have their partner use) acceptable contraception during heterosexual activity during the treatment period and for at least 120 days after the last dose of study treatment.

You may not qualify if:

• Has oligo-secretory myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström's macroglobulinemia, or any history of plasma cell leukemia.
• Has a history of repeated infections, primary amyloidosis, hyperviscosity, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Has known meningeal involvement of MM.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or daratumumab and any of its excipients.
• Has known allergies, hypersensitivity, or intolerance to monoclonal antibodies (mAbs) or human proteins, or their excipients, or known sensitivity to mammalian-derived products.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has either of the following: a.) Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal, or b.) Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of hepatitis B or known active hepatitis C.
• Has a known history of active tuberculosis (TB).
• Has received prior solid organ transplant.
• Has clinically significant cardiac disease or electrocardiogram (ECG) abnormalities or any history of clinically significant ventricular arrhythmias.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (23)

Mayo Clinic Jacksonville ( Site 0003)

Jacksonville, Florida, 32224, United States

Location

Emory University School of Medicine ( Site 0002)

Atlanta, Georgia, 30322, United States

Location

Karmanos Cancer Institute ( Site 0001)

Bloomfield Hills, Michigan, 48302, United States

Location

Calgary Lab Services - Foothills Medical Centre ( Site 0105)

Calgary, Alberta, H9H 4M7, Canada

Location

Cross Cancer Institute ( Site 0104)

Edmonton, Alberta, H9H 4M7, Canada

Location

Capital Health Queen Elizabeth II Health Sciences Centre ( Site 0101)

Halifax, Nova Scotia, H9H 4M7, Canada

Location

Hopital Maisonneuve-Rosemont [Montreal, Canada] ( Site 0102)

Montreal, Quebec, H9H 4M7, Canada

Location

McGill University Health Centre ( Site 0100)

Montreal, Quebec, H9H 4M7, Canada

Location

CHU de Quebec - Hopital de l'Enfant-Jesus ( Site 0106)

Québec, Quebec, H9H 4M7, Canada

Location

CHRU Lille Hospital Claude Huriez ( Site 0200)

Lille, France

Location

Hopital Saint-Louis ( Site 0202)

Paris, France

Location

Centre Hopitalier Lyon Sud ( Site 0201)

Pierre-Bénite, France

Location

Rambam Medical Center ( Site 0700)

Haifa, Israel

Location

Rabin Medical Center ( Site 0702)

Petah Tikva, Israel

Location

Sourasky Medical Center ( Site 0701)

Tel Aviv, Israel

Location

Sheba MC ( Site 0703)

Tel Litwinsky, Israel

Location

Hospital Universitari Germans Trias i Pujol ( Site 0302)

Badalona, Spain

Location

Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0303)

L'Hospitalet de Llobregat, Spain

Location

Clinica Universitaria de Navarra ( Site 0301)

Pamplona, Spain

Location

Hospital Clinico Universitario de Salamanca ( Site 0300)

Salamanca, Spain

Location

Hospital Clinico Universitario de Valencia ( Site 0304)

Valencia, Spain

Location

Skaenes Universitetssjukhus Lund ( Site 0500)

Lund, Sweden

Location

Karolinska Universitetssjukhuset ( Site 0501)

Stockholm, Sweden

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 18, 2017
• Study Start: August 1, 2017
• Primary Completion: March 20, 2019
• Study Completion: June 10, 2021
• Last Updated: March 25, 2019

Record last verified: 2019-03

Locations

ES (5); CA (6); FR (3); IL (4); SE (2); US (3)