Clinical trial NCT02576977: Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183)
Official title: A Phase III Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (KEYNOTE 183)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: PDL1
PD1
Multiple Myeloma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-10-15
Enrollment: 251
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 pomalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of pomalidomide and low dose dexamethasone without pembrolizumab in terms of Progression-Free Survival (PFS) in participants with refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least 2 lines of prior treatment. The study's 2 primary hypotheses are: 1. Pembrolizumab in combination with pomalidomide and low dose dexamethasone prolongs PFS as assessed by Clinical Adjudication Committee (CAC) blinded central review using International Myeloma Working Group Criteria for Response Assessment in Multiple Myeloma (IMWG) criteria compared to treatment with pomalidomide and low dose dexamethasone standard of care (SOC) alone. 2. Pembrolizumab in combination with pomalidomide and low dose dexamethasone prolongs OS compared to treatment with pomalidomide and low dose dexamethasone (SOC) alone.


Eligibility criteria: Inclusion Criteria:

* Has a confirmed diagnosis of active multiple myeloma and measurable disease
* Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)
* Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD) AND proteasome inhibitor alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor
* Has performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Female participants of childbearing potential must have 2 negative urine human chorionic gonadotropin tests within 10 to 14 days and within 24 hours prior to receiving study medication
* Female participants of childbearing potential and male participants must agree to use adequate contraception 28 days prior to study start and continuing for up to 28 days after the last dose of pomalidomide (or 120 days after the last dose of pembrolizumab)

Exclusion Criteria:

* Has had prior anti-myeloma therapy within 2 weeks prior to study start and has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events due to a previously administered agent
* Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease \[GVHD\]).
* Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first infusion or is planning for or is eligible for auto-SCT
* Has received previous therapy with pomalidomide
* 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 a 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), antiprogrammed 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 costimulation or checkpoint pathways)
* Is pregnant or breast-feeding

Primary outcomes:
measure: Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria
timeFrame: Up to approximately 30 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 54 months
Secondary outcomes:
measure: Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
timeFrame: Up to approximately 30 months
measure: Participants Experiencing One or More Adverse Events (AEs)
timeFrame: Up to approximately 54 months
measure: Participants Discontinuing Study Investigational Product Due to an AE
timeFrame: Up to approximately 54 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 30 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Liao JJZ, Farooqui MZH, Marinello P, Hartzel J, Anderson K, Ma J, Gause CK. Using artificial intelligence tools in answering important clinical questions: The KEYNOTE-183 multiple myeloma experience. Contemp Clin Trials. 2020 Dec;99:106179. doi: 10.1016/j.cct.2020.106179. Epub 2020 Oct 18.
citation: Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, Goldschmidt H, Larocca A, Chanan-Khan A, Sherbenou D, Avivi I, Benyamini N, Iida S, Matsumoto M, Suzuki K, Ribrag V, Usmani SZ, Jagannath S, Ocio EM, Rodriguez-Otero P, San Miguel J, Kher U, Farooqui M, Liao J, Marinello P, Lonial S; KEYNOTE-183 Investigators. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019 Sep;6(9):e459-e469. doi: 10.1016/S2352-3026(19)30110-3. Epub 2019 Jul 18.