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)

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02576977
• Other study ID #: 3475-183
• Secondary ID: 2015-002509-1316
• Status: Terminated
• Phase: Phase 3
• Start date: October 19, 2015
• Est. completion date: July 16, 2020

Study information

• Verified date: September 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 251
• Est. completion date: July 16, 2020
• Est. primary completion date: July 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• Pembrolizumab
pembrolizumab 200 mg IV infusion

Drug:
• Pomalidomide
pomalidomide 4 mg capsules
• Dexamethasone
dexamethasone 40 mg tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria	Progression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was July 9, 2018.	Up to approximately 30 months
Primary	Overall Survival (OS)	Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Median overall survival was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was August 3, 2020.	Up to approximately 54 months
Secondary	Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review	ORR was defined as the percentage of the participants in the analysis population who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR = 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = =50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by =90% or to <200 mg/24 hours. The database cutoff date was July 9, 2018.	Up to approximately 30 months
Secondary	Participants Experiencing One or More Adverse Events (AEs)	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Database cutoff was August 3, 2020.	Up to approximately 54 months
Secondary	Participants Discontinuing Study Investigational Product Due to an AE	An adverse event was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Database cutoff was August 3, 2020.	Up to approximately 54 months
Secondary	Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review	Disease control rate was the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR = 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = =50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by =90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.	Up to approximately 30 months
Secondary	Second Progression Free Survival (PFS2)	PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. As a result of a full clinical hold by FDA that led to discontinuation of study enrollment, no data was collected for analysis of PFS2.	Up to approximately 30 months

External Links

•   Merck Oncology Clinical Trials Information