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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03221634
• Date of registration: 17/07/2017
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: Efficacy and Safety Study of Pembrolizumab (MK-3475) in Combination With Daratumumab in Participants With Relapsed Refractory Multiple Myeloma (MK-3475-668/KEYNOTE-668)
• Scientific title: A Phase 2 Study of Pembrolizumab in Combination With Daratumumab (Anti CD38) in Participants With Relapsed Refractory Multiple Myeloma (rrMM)
• Date of first enrolment: August 1, 2017
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03221634
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, France, Israel, Norway, Spain, Sweden, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme Corp.

Key inclusion & exclusion 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 ?/?) 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Biological: Pembrolizumab

Biological: Daratumumab

Primary Outcome(s)

Objective Response Rate (ORR) [Time Frame: Up to approximately 2 years]

Secondary Outcome(s)

Adverse Events (AEs) [Time Frame: Up to approximately 27 months]

Disease Control Rate (DCR) [Time Frame: Up to approximately 2 years]

Study Treatment Discontinuations Due to AEs [Time Frame: Up to approximately 2 years]

Duration of Response (DOR) [Time Frame: Up to approximately 2 years]

Secondary ID(s)

3475-668

2017-001001-32

Source(s) of Monetary Support

Please refer to primary and secondary sponsors