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

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ClinicalTrials.gov Identifier: NCT03221634
Recruitment Status : Not yet recruiting
First Posted : July 18, 2017
Last Update Posted : July 18, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: Pembrolizumab Biological: Daratumumab Phase 2

Detailed Description:
Study treatment will continue until the participant has completed 35 infusions (approximately 2 years) of pembrolizumab treatment. All participants who stop study treatment with stable disease (SD) or better may be eligible for up to an additional ~1 year of study treatment if they progress after stopping study treatment from the initial treatment phase.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Pembrolizumab in Combination With Daratumumab (Anti CD38) in Participants With Relapsed Refractory Multiple Myeloma (rrMM)
Estimated Study Start Date : August 1, 2017
Estimated Primary Completion Date : March 20, 2019
Estimated Study Completion Date : June 10, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Pembrolizumab
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
IV infusion
Other Name: MK-3475

Biological: Daratumumab
IV infusion
Other Name: DARZALEX®




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
    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.


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: Up to approximately 2 years ]
    DCR is defined as the percentage of participants who experience stable disease (SD; not meeting criteria for complete response, very good partial response, partial response, minimal response or progressive disease) or better prior to any evidence of progression, per IMWG 2016 based on investigator assessment.

  2. Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    DOR is defined as the time from first documented evidence of at least a PR (≥50% reduction of serum M-protein plus reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours) until disease progression or death, per IMWG 2016, based on investigator assessment.

  3. Adverse Events (AEs) [ Time Frame: Up to approximately 27 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing one or more AEs will be assessed.

  4. Study Treatment Discontinuations Due to AEs [ Time Frame: Up to approximately 2 years ]
    The number of participants discontinuing study treatment due to AEs will be assessed.



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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
  • Has previously received daratumumab or other anti-cluster of differentiation 38 (anti-CD38) therapies.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK-3475) clinical study.
  • Has received prior anti-myeloma therapy including but not limited to dexamethasone, IMiDs, PIs, monoclonal antibody, chemotherapy, or radiation therapy within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (≤ Grade 1 or at Baseline) from AEs due to previously administered agents.
  • Has undergone prior allogeneic stem cell transplant (allo-SCT) within the last 5 years.
  • Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first dose of study treatment or are planning for or are eligible for auto- or allo-SCT.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03221634


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
United States, Florida
Mayo Clinic Jacksonville ( Site 0003) Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Study Coordinator    904-953-2607      
United States, Georgia
Emory University School of Medicine ( Site 0002) Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Study Coordinator    404-778-1900      
United States, Michigan
Karmanos Cancer Institute ( Site 0001) Not yet recruiting
Bloomfield Hills, Michigan, United States, 48302
Contact: Study Coordinator    313-576-8730      
Canada, Alberta
Calgary Lab Services - Foothills Medical Centre ( Site 0105) Not yet recruiting
Calgary, Alberta, Canada, H9H 4M7
Contact: Study Coordinator    4039441564      
Cross Cancer Institute ( Site 0104) Not yet recruiting
Edmonton, Alberta, Canada, H9H 4M7
Contact: Study Coordinator    7804328757      
Canada, Nova Scotia
Capital Health Queen Elizabeth II Health Sciences Centre ( Site 0101) Not yet recruiting
Halifax, Nova Scotia, Canada, H9H 4M7
Contact: Study Coordinator    9024734642      
Canada, Quebec
Hopital Maisonneuve-Rosemont [Montreal, Canada] ( Site 0102) Not yet recruiting
Montreal, Quebec, Canada, H9H 4M7
Contact: Study Coordinator    51425234004471      
McGill University Health Centre ( Site 0100) Not yet recruiting
Montreal, Quebec, Canada, H9H 4M7
Contact: Study Coordinator    5148431558      
Canada
CHU de Quebec - Hopital de l'Enfant-Jesus ( Site 0106) Not yet recruiting
Quebec, Canada, H9H 4M7
Contact: Study Coordinator    418525444463115      
France
Clinique Louis Pasteur ( Site 0203) Withdrawn
Essey-les-Nancy, France
CHRU Lille Hospital Claude Huriez ( Site 0200) Not yet recruiting
Lille, France
Contact: Study Coordinator    +33320445712      
Hopital Saint-Louis ( Site 0202) Not yet recruiting
Paris, France
Contact: Study Coordinator    +33142499472      
Centre Hopitalier Lyon Sud ( Site 0201) Not yet recruiting
Pierre Benite, France
Contact: Study Coordinator    +33478864309      
Israel
Rambam Medical Center ( Site 0700) Not yet recruiting
Haifa, Israel
Contact: Study Coordinator    +97248542541      
Rabin Medical Center ( Site 0702) Not yet recruiting
Petah-Tikva, Israel
Contact: Study Coordinator    +972504065462      
Sourasky Medical Center ( Site 0701) Not yet recruiting
Tel Aviv, Israel
Contact: Study Coordinator    +97236973782      
Sheba MC ( Site 0703) Not yet recruiting
Tel Hashomer, Israel
Contact: Study Coordinator    +97235305830      
Norway
Oslo Universitetssykehus HF, Rikshospitalet ( Site 0600) Withdrawn
Oslo, Norway
Spain
Hospital Universitari Germans Trias i Pujol ( Site 0302) Not yet recruiting
Badalona, Spain
Contact: Study Coordinator    +34934978987      
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0303) Not yet recruiting
Hospitalet de Llobregat, Spain
Contact: Study Coordinator    +34932607750      
Clinica Universitaria de Navarra ( Site 0301) Not yet recruiting
Pamplona, Spain
Contact: Study Coordinator    +34948296397      
Hospital Clinico Universitario de Salamanca ( Site 0300) Not yet recruiting
Salamanca, Spain
Contact: Study Coordinator    +34923292100      
Hospital Clinico Universitario de Valencia ( Site 0304) Not yet recruiting
Valencia, Spain
Contact: Study Coordinator    +34637520820      
Sweden
Skaenes Universitetssjukhus Lund ( Site 0500) Not yet recruiting
Lund, Sweden
Contact: Study Coordinator    +46462220737      
Karolinska Universitetssjukhuset ( Site 0501) Not yet recruiting
Stockholm, Sweden
Contact: Study Coordinator    +46858580000      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03221634     History of Changes
Other Study ID Numbers: 3475-668
2017-001001-32 ( EudraCT Number )
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: July 18, 2017
Last Verified: July 2017

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

Keywords provided by Merck Sharp & Dohme Corp.:
Programmed cell death 1 receptor (PD1)
PD-1
Programmed cell death ligand 1 receptor (PDL1)
PD-L1

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs