Clinical trial NCT03221634: Efficacy and Safety Study of Pembrolizumab (MK-3475) in Combination With Daratumumab in Participants With Relapsed Refractory Multiple Myeloma (MK-3475-668/KEYNOTE-668)
Official title: A Phase 2 Study of Pembrolizumab in Combination With Daratumumab (Anti CD38) in Participants With Relapsed Refractory Multiple Myeloma (rrMM)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Programmed cell death 1 receptor (PD1)
PD-1
Programmed cell death ligand 1 receptor (PDL1)
PD-L1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-07-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Adverse Events (AEs)
timeFrame: Up to approximately 27 months
measure: Study Treatment Discontinuations Due to AEs
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville ( Site 0003)
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine ( Site 0002)
state: Georgia
city: Bloomfield Hills
country: United States
facility: Karmanos Cancer Institute ( Site 0001)
state: Michigan
city: Calgary
country: Canada
facility: Calgary Lab Services - Foothills Medical Centre ( Site 0105)
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0104)
state: Alberta
city: Halifax
country: Canada
facility: Capital Health Queen Elizabeth II Health Sciences Centre ( Site 0101)
state: Nova Scotia
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont [Montreal, Canada] ( Site 0102)
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre ( Site 0100)
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec - Hopital de l'Enfant-Jesus ( Site 0106)
city: Lille
country: France
facility: CHRU Lille Hospital Claude Huriez ( Site 0200)
city: Paris
country: France
facility: Hopital Saint-Louis ( Site 0202)
city: Pierre Benite
country: France
facility: Centre Hopitalier Lyon Sud ( Site 0201)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0700)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center ( Site 0702)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0701)
city: Tel Hashomer
country: Israel
facility: Sheba MC ( Site 0703)
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ( Site 0302)
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0303)
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra ( Site 0301)
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca ( Site 0300)
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia ( Site 0304)
city: Lund
country: Sweden
facility: Skaenes Universitetssjukhus Lund ( Site 0500)
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset ( Site 0501)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: