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)

Terminated Phase 3 Results posted Last updated 8 October 2021

What this trial tests

Phase 3 trial testing Pembrolizumab in Multiple Myeloma in 251 participants. Terminated before completion.

Timeline

19 October 2015

Primary endpoint
9 July 2018

16 July 2020

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	251
Start date	19 October 2015
Primary completion	9 July 2018
Estimated completion	16 July 2020

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →
• Pomalidomide — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Multiple Myeloma — all drugs for Multiple Myeloma →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria Primary · Up to approximately 30 months

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.

Group	Value	95% CI
Pembrolizumab+Pomalidomide+Dexamethasone	5.7	4.5 – 7.5
Standard of Care (SOC) Pomalidomide+Dexamethasone	7.4	5.6 – 11.5

Overall Survival (OS) Primary · Up to approximately 54 months

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.

Group	Value	95% CI
Pembrolizumab+Pomalidomide+Dexamethasone	21.0	14.2 – 29.1
Standard of Care (SOC) Pomalidomide+Dexamethasone	39.6	28.5 – NA

Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review Secondary · Up to approximately 30 months

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; VG

Group	Value	95% CI
Pembrolizumab+Pomalidomide+Dexamethasone	37.3	28.9 – 46.4
Standard of Care (SOC) Pomalidomide+Dexamethasone	42.4	33.6 – 51.6

Participants Experiencing One or More Adverse Events (AEs) Secondary · Up to approximately 54 months

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.

Group	Value	95% CI
Pembrolizumab+Pomalidomide+Dexamethasone	122
Standard of Care (SOC) Pomalidomide+Dexamethasone	119

Participants Discontinuing Study Investigational Product Due to an AE Secondary · Up to approximately 54 months

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.

Group	Value	95% CI
Pembrolizumab+Pomalidomide+Dexamethasone	26
Standard of Care (SOC) Pomalidomide+Dexamethasone	10

Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review Secondary · Up to approximately 30 months

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 immunohistochemis

Group	Value	95% CI
Pembrolizumab+Pomalidomide+Dexamethasone	88.1	81.1 – 93.2
Standard of Care (SOC) Pomalidomide+Dexamethasone	84.8	77.3 – 90.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 54 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab+Pomalidomide+Dexamethasone

Serious: 79/122 (65%)

Deaths: 86/126

Standard of Care (SOC) Pomalidomide+Dexamethasone

Serious: 57/123 (46%)

Deaths: 64/125

Serious adverse events (134 terms)

Reaction	System	Pembrolizumab+Pomalidomide…	Standard of Care (SOC) Pom…
Pneumonia	Infections and infestations	—	—
Pyrexia	General disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Death	General disorders	—	—
Influenza	Infections and infestations	—	—
Pneumocystis jirovecii pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Pathological fracture	Musculoskeletal and connective tissue disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Fatigue	General disorders	—	—
Cellulitis	Infections and infestations	—	—
Neutropenic sepsis	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Neutrophil count decreased	Investigations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Renal failure	Renal and urinary disorders	—	—

Other adverse events (45 terms — click to expand)

Reaction	System	Pembrolizumab+Pomalidomide…	Standard of Care (SOC) Pom…
Neutropenia	Blood and lymphatic system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Nausea	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Neutrophil count decreased	Investigations	—	—
Insomnia	Psychiatric disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Asthenia	General disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
White blood cell count decreased	Investigations	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Tremor	Nervous system disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Chest pain	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Neuropathy peripheral	Nervous system disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Blood creatinine increased	Investigations	—	—
Weight decreased	Investigations	—	—

Most-reported serious reactions: Pneumonia, Pyrexia, Pneumonitis, Anaemia, Febrile neutropenia, Acute kidney injury, Pulmonary embolism, Death.

Data from ClinicalTrials.gov NCT02576977 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
   Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
2. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
   Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
3. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial.
   Mateos MV, Blacklock H, Schjesvold F, Oriol A, et al · · 2019 · cited 195× · PMID 31327687 · DOI 10.1016/s2352-3026(19)30110-3
4. The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?
   Franzin R, Netti GS, Spadaccino F, Porta C, et al · · 2020 · cited 142× · PMID 33162990 · DOI 10.3389/fimmu.2020.574271
5. Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies.
   Wang H, Kaur G, Sankin AI, Chen F, et al · · 2019 · cited 138× · PMID 31186046 · DOI 10.1186/s13045-019-0746-1
6. Checkpoint inhibitors in hematological malignancies.
   Ok CY, Young KH. · · 2017 · cited 93× · PMID 28482851 · DOI 10.1186/s13045-017-0474-3
7. Targeting immune checkpoints in hematological malignancies.
   Salik B, Smyth MJ, Nakamura K. · · 2020 · cited 92× · PMID 32787882 · DOI 10.1186/s13045-020-00947-6
8. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma.
   Jelinek T, Paiva B, Hajek R. · · 2018 · cited 82× · PMID 30505301 · DOI 10.3389/fimmu.2018.02431