Clinical trial NCT02579863: Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185)
Official title: A Phase III Study of Lenalidomide and Low-Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Newly Diagnosed and Treatment Naïve Multiple Myeloma (KEYNOTE 185).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: PD1
PD-1
PD-L1
PDL1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-10-20
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy of lenalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of lenalidomide and low dose dexamethasone without pembrolizumab in terms of progression-free survival (PFS) in participants with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT). The study's primary hypothesis is that pembrolizumab in dexamethasone prolongs progression free survival (PFS) as assessed by Clinical Adjudication Committee (CAC) blinded central review using International Myeloma Working Group (IMWG) response criteria compared to treatment combination with lenalidomide and low-dose with lenalidomide and low-dose dexamethasone (standard of care, SOC) alone.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of active multiple myeloma and measurable disease.
* Ineligible to receive treatment with auto-SCT due to age (≥65 years old) or any significant coexisting medical condition (cardiac, renal, pulmonary or hepatic dysfunction), likely to have a negative impact on tolerability of auto-SCT. Participants \<65 years of age who refuse auto-SCT are not eligible for this study.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Female participants of childbearing potential must have 2 negative urine pregnancy tests (with a sensitivity of at least 25 Milli-international units/milliliter) within 10 to 14 days and within 24 hours prior to receiving study medication.
* Female participants of childbearing potential must agree to use adequate contraception 28 days prior to study start, continuing throughout the study, and for up to 28 days after the last dose of lenalidomide (or 120 days after the last dose of pembrolizumab).
* Male participants of childbearing potential must agree to use adequate contraception from the first dose of study medication, continuing throughout the study, and for up to 28 days after the last dose of lenalidomide (or 120 days after the last dose of pembrolizumab).

Exclusion Criteria:

* Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years.
* Has peripheral neuropathy ≥ Grade 2.
* Has a known additional malignancy that is progressing or requires active treatment within the last 5 years (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
* Has history of non-infectious pneumonitis that required steroids or current pneumonitis
* Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), anti-programmed 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 a known Human Immunodeficiency Virus (HIV), or a known, active Hepatitis B (HBV), or a known, active Hepatitis C (HCV) infection.
* Is unable or unwilling to undergo thromboembolic prophylaxis including, as clinically indicated, aspirin, Coumadin (warfarin) or low-molecular weight heparin.
* Has lactose intolerance.
* Has an invasive fungal infection.

Primary outcomes:
measure: Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review
timeFrame: Up to approximately 30 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 55 months
measure: Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
timeFrame: Up to approximately 30 months
measure: Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review
timeFrame: Up to approximately 30 months
measure: Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
timeFrame: Up to approximately 30 months
measure: Second Progression Free Survival (PFS2)
timeFrame: Up to approximately 55 months
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to approximately 55 months
measure: Number of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to approximately 55 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, Yimer HA, LeBlanc R, Takezako N, McCroskey RD, Lim ABM, Suzuki K, Kosugi H, Grigoriadis G, Avivi I, Facon T, Jagannath S, Lonial S, Ghori RU, Farooqui MZH, Marinello P, San-Miguel J; KEYNOTE-185 Investigators. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019 Sep;6(9):e448-e458. doi: 10.1016/S2352-3026(19)30109-7. Epub 2019 Jul 18.