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)

NCT02576977 | Terminated Phase 3 Results DMC FDA Drug

• 5 other identifiers: 3475-1832015-002509-13163146MK-3475-183KEYNOTE-183
• Study Type: interventional
• Target: 251
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Myeloma

Keywords

PDL1; PD1; Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review

  Up to approximately 30 months

• Participants Experiencing One or More Adverse Events (AEs)

  Up to approximately 54 months

• Participants Discontinuing Study Investigational Product Due to an AE

  Up to approximately 54 months

• Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review

  Up to approximately 30 months

• Second Progression Free Survival (PFS2)

  Up to approximately 30 months

Study Arms (2)

Pembrolizumab+Pomalidomide+Dexamethasone

EXPERIMENTAL

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.

Biological: Pembrolizumab; Drug: Pomalidomide; Drug: Dexamethasone

Pomalidomide+Dexamethasone

ACTIVE COMPARATOR

Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.

Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Pembrolizumab BIOLOGICAL

pembrolizumab 200 mg IV infusion

Also known as: KEYTRUDA®, MK-3475, SCH 9000475

Pembrolizumab+Pomalidomide+Dexamethasone

Pomalidomide DRUG

pomalidomide 4 mg capsules

Also known as: POMALYST®

Pembrolizumab+Pomalidomide+Dexamethasone; Pomalidomide+Dexamethasone

Dexamethasone DRUG

dexamethasone 40 mg tablets

Pembrolizumab+Pomalidomide+Dexamethasone; Pomalidomide+Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 33086159 DERIVED

• 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.

  PMID: 31327687 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

The MK-3475-183 study was stopped/terminated early. Endpoint statistics may be biased due to the incomplete treatment and follow-up of participants after study termination

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2015
• First Posted: October 15, 2015
• Study Start: October 19, 2015
• Primary Completion: July 9, 2018
• Study Completion: July 16, 2020
• Last Updated: October 8, 2021
• Results First Posted: August 2, 2019

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share