Multiple MyelomaPhase 1NCT02036502
A Study of Pembrolizumab (MK-3475) in Combination With Standard of Care Treatments in Participants With Multiple Myeloma (MK-3475-023/KEYNOTE-023)
A Phase 1 study testing Pembrolizumab, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Merck Sharp & Dohme LLC.
Trial summary
This is a study of pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory Multiple Myeloma (rrMM), and in combination with carfilzomib and low-dose dexamethasone in participants with relapsed or refractory Multiple Myeloma (rMM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Pembrolizumab, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- No sites listed yet
- Study dates
- 14 Feb 2014to 19 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Participants:
- Confirmed diagnosis of multiple myeloma (MM)
- MM with measurable disease
- Archival or newly obtained bone marrow material available. In addition, for participants in the United States (US) and Canada, able to provide newly obtained bone marrow aspirate for biomarker analysis.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
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- Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
- Male participants must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study treatment through 120 days after the last dose of study treatment
- Able to swallow capsules and able to take or tolerate oral medications on a continuous basis
- Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:
- Must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy and must have failed their last line of treatment
- Prior anti-myeloma treatments must have included an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor
- Must agree to follow the regional requirements for lenalidomide counseling, pregnancy testing, and birth control; willing and able to comply with the regional requirements (for example, periodic pregnancy tests and safety labs)
- Cohort 2 Participants:
- MM with relapsing or refractory disease at study entry
- Received prior treatment with 1 to 3 lines for MM
- Achieved a partial response to at least one prior regimen (defined as ≥50% decrease in tumor burden)
- Left ventricular ejection fraction of at least 40%
Who cannot join
- All Participants:
- Currently participating in and receiving study therapy or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
- History of repeated infections; primary amyloidosis; hyperviscosity; plasma cell leukemia; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or Waldenström's macroglobulinemia
- Diagnosis of immunosuppressive disorder or on any other immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Received a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from a baseline AE or a Grade 1 AE associated with agents administered more than 4 weeks earlier
- Prior anti-MM therapy (including dexamethasone), targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent
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- An additional malignancy that is progressing or requires active treatment within the last 5 years
- Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Active infection requiring intravenous systemic therapy
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment
- Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
- Clinically significant coagulopathy
- Has had or is planning for allogeneic stem cell transplant
- Autologous stem cell transplant within 12 weeks before the first infusion
- History of Grade 4 rash associated with thalidomide treatment
- Known hypersensitivity to thalidomide, lenalidomide or pomalidomide
- Received a live vaccine within 30 days of planned start of study treatment
- Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:
- Clinically active central nervous system (CNS) involvement
- Known gastrointestinal disease that may significantly alter the absorption of lenalidomide
- Unable or unwilling to undergo antithrombotic prophylactic treatment
- Known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- Cohort 2 Participants:
- Smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia
- Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to the first dose of study treatment
- Myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker.
- Known history of allergy to CAPTISOL® (a cyclodextrin derivative used to solubilize carfilzomib)
- Hypersensitivity to carfilzomib, bortezomib, boron, or mannitol
- Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first dose of study treatment
- Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to the first dose of study treatment
About this study
Official title: A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination With Backbone Treatments for Subjects With Multiple Myeloma
This is a study of pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory Multiple Myeloma (rrMM), and in combination with carfilzomib and low-dose dexamethasone in participants with relapsed or refractory Multiple Myeloma (rMM).
This study was being done to find the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D), and to evaluate the safety and tolerability of pembrolizumab when given in combination with standard of care (SOC) treatments in participants with rrMM or rMM. Preliminary efficacy data will also be assessed. There was no primary hypothesis associated with this study.
Read more
On 03-Jul-2017, the United States Food and Drug Administration (US FDA) placed the rrMM cohort of this protocol on clinical hold based on safety data from two other pembrolizumab protocols: MK-3475-183 (NCT02576977) and MK-3475-185 (NCT02579863) presented to the Data Monitoring Committee.
On 15-Sep-2017, the US FDA placed the rMM cohort of this study on partial clinical hold. Enrollment was stopped and will not be reopened. Participants who are deriving clinical benefit were allowed to continue receiving study treatment until protocol-specific end of treatment, and then progress into long term safety and survival follow up. Participants who are not deriving clinical benefit, must stop study treatment and move into the long term safety and survival follow up.
- Conditions
- Multiple Myeloma
- Being tested
- Pembrolizumab, Lenalidomide, Dexamethasone, Carfilzomib
- Keywords
- PD1, PD-1, PDL1, PD-L1
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
Intravenous (IV) infusion
LenalidomideDrug
Also called REVLIMID®
Oral capsule
DexamethasoneDrug
Also called DECADRON®
Oral tablet IV infusion
CarfilzomibDrug
Also called KYPROLIS®
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1:pembro 2mg/kg+len 25mg+dex 40 mg | Experimental | Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 1:pembro 2mg/kg+len 10 mg+dex 40 mg | Experimental | Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 2:pembro 200 mg+len 25 mg+dex 40 mg | Experimental | Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 2:pembro 200 mg+len 25 mg+dex 20 mg | Experimental | Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28- day cycle). Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 2:pembro 200 mg+len 10 mg+dex 40 mg | Experimental | Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 3:pembro 200 mg+len 25 mg+dex 40 mg | Experimental | Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W weekly during each 28-day cycle. Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 3:pembro 200 mg+len 25 mg+dex 20 mg | Experimental | Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W weekly during each 28-day cycle. Receives: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Part 3:pembro 200 mg+carf 56 mg/m^2+dex 20 mg | Experimental | Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg once or twice weekly (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Receives: Biological: Pembrolizumab; Drug: Dexamethasone; Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
DLTs were assessed during Cycle 1 (28 days) and were defined as the occurrence of any of the following judged by the investigator to be possibly, probably or definitely related to study drug: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days; Gr 3 non-hematologic toxicity lasting >3 days; Gr 3 non-hematologic laboratory value if: medical intervention was required, abnormality led to hospitalization, was renal or liver function related, or persisted for >1 week; Gr 3/4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (associated with bleeding requiring platelet transfusion or life-threatening bleeding); Gr 5 toxicity; or delay of >1 week in initiating Cycle 2 or unable to complete 80% of treatment during the first course of therapy due to drug-related toxicity. DLTs for the rMM cohort were any drug-related adverse events that cannot be managed by dose modification. DLTs are reported for the maximum tolerated dose.
Measured: Up to 28 days in Cycle 1
Number of Participants Who Experienced One or More Adverse Events (AEs)
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.
Measured: Up to approximately 72.7 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.
Measured: Up to approximately 72.7 months
Secondary outcomes (2)
Objective Response Rate (ORR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
ORR was the percentage of the participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs.
Measured: Up to approximately 72.7 months
Disease Control Rate (DCR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
DCR was the percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or stable disease (SD) ≥12 weeks prior to evidence of disease progression (PD). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+ ≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not on electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR=≥50% reduction of serum M-protein+reduction in 24 hr urinary M-protein by ≥90% or to <200 mg/24 hrs; SD=not meeting the criteria for CR, VGPR, PR, or PD. PD=≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas.
Measured: Up to approximately 72.7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2014 (estimated)
- Study start14 Feb 2014
- Primary completion19 Mar 2020
- Study completion19 Mar 2020
Why it stopped: Business Reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02036502
- Sponsor's protocol ID
- 3475-023
- Other IDs
- 2013-003512-44, MK-3475-023, KEYNOTE-023
- Status last verified
- Mar 2021
- First submitted
- 13 Jan 2014
- Last updated
- 8 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Mateos MV, Orlowski RZ, Ocio EM, Rodriguez-Otero P, Reece D, Moreau P, Munshi N, Avigan DE, Siegel DS, Ghori R, Farooqui MZH, Marinello P, San-Miguel J. Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol. 2019 Sep;186(5):e117-e121. doi: 10.1111/bjh.15946. Epub 2019 May 15. No abstract available.
PubMed 31090915
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination With Backbone Treatments for Subjects With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02036502
- Acronym / sponsor ID
- 3475-023
- Conditions
- Multiple Myeloma
- Keywords
- PD1, PD-1, PDL1, PD-L1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Reasons
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2014 (actual)
- Primary completion
- 19 Mar 2020 (actual)
- Study completion
- 19 Mar 2020 (actual)
- First posted
- 15 Jan 2014 (estimated)
- Results
- Posted 8 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study of pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory Multiple Myeloma (rrMM), and in combination with carfilzomib and low-dose dexamethasone in participants with relapsed or refractory Multiple Myeloma (rMM).
This study was being done to find the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D), and to evaluate the safety and tolerability of pembrolizumab when given in combination with standard of care (SOC) treatments in participants with rrMM or rMM. Preliminary efficacy data will also be assessed. There was no primary hypothesis associated with this study.
On 03-Jul-2017, the United States Food and Drug Administration (US FDA) placed the rrMM cohort of this protocol on clinical hold based on safety data from two other pembrolizumab protocols: MK-3475-183 (NCT02576977) and MK-3475-185 (NCT02579863) presented to the Data Monitoring Committee.
On 15-Sep-2017, the US FDA placed the rMM cohort of this study on partial clinical hold. Enrollment was stopped and will not be reopened. Participants who are deriving clinical benefit were allowed to continue receiving study treatment until protocol-specific end of treatment, and then progress into long term safety and survival follow up. Participants who are not deriving clinical benefit, must stop study treatment and move into the long term safety and survival follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part 1:pembro 2mg/kg+len 25mg+dex 40 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). |
| Part 1:pembro 2mg/kg+len 10 mg+dex 40 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). |
| Part 2:pembro 200 mg+len 25 mg+dex 40 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). |
| Part 2:pembro 200 mg+len 25 mg+dex 20 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28- day cycle). |
| Part 2:pembro 200 mg+len 10 mg+dex 40 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). |
| Part 3:pembro 200 mg+len 25 mg+dex 40 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W weekly during each 28-day cycle. |
| Part 3:pembro 200 mg+len 25 mg+dex 20 mg | Experimental | Biological: Pembrolizumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W weekly during each 28-day cycle. |
| Part 3:pembro 200 mg+carf 56 mg/m^2+dex 20 mg | Experimental | Biological: Pembrolizumab, Drug: Dexamethasone, Drug: CarfilzomibParticipants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg once or twice weekly (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Confirmed diagnosis of multiple myeloma (MM)
- MM with measurable disease
- Archival or newly obtained bone marrow material available. In addition, for participants in the United States (US) and Canada, able to provide newly obtained bone marrow aspirate for biomarker analysis.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
Key exclusion criteria (34 listed)
- Currently participating in and receiving study therapy or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
- History of repeated infections; primary amyloidosis; hyperviscosity; plasma cell leukemia; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or Waldenström's macroglobulinemia
- Diagnosis of immunosuppressive disorder or on any other immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Received a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from a baseline AE or a Grade 1 AE associated with agents administered more than 4 weeks earlier
- Prior anti-MM therapy (including dexamethasone), targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475, KEYTRUDA®Intravenous (IV) infusion | Biological | Part 1:pembro 2mg/kg+len 10 mg+dex 40 mg, Part 1:pembro 2mg/kg+len 25mg+dex 40 mg, Part 2:pembro 200 mg+len 10 mg+dex 40 mg, Part 2:pembro 200 mg+len 25 mg+dex 20 mg, Part 2:pembro 200 mg+len 25 mg+dex 40 mg, Part 3:pembro 200 mg+carf 56 mg/m^2+dex 20 mg, Part 3:pembro 200 mg+len 25 mg+dex 20 mg, Part 3:pembro 200 mg+len 25 mg+dex 40 mg |
| LenalidomideAlso: REVLIMID®Oral capsule | Drug | Part 1:pembro 2mg/kg+len 10 mg+dex 40 mg, Part 1:pembro 2mg/kg+len 25mg+dex 40 mg, Part 2:pembro 200 mg+len 10 mg+dex 40 mg, Part 2:pembro 200 mg+len 25 mg+dex 20 mg, Part 2:pembro 200 mg+len 25 mg+dex 40 mg, Part 3:pembro 200 mg+len 25 mg+dex 20 mg, Part 3:pembro 200 mg+len 25 mg+dex 40 mg |
| DexamethasoneAlso: DECADRON®Oral tablet IV infusion | Drug | Part 1:pembro 2mg/kg+len 10 mg+dex 40 mg, Part 1:pembro 2mg/kg+len 25mg+dex 40 mg, Part 2:pembro 200 mg+len 10 mg+dex 40 mg, Part 2:pembro 200 mg+len 25 mg+dex 20 mg, Part 2:pembro 200 mg+len 25 mg+dex 40 mg, Part 3:pembro 200 mg+carf 56 mg/m^2+dex 20 mg, Part 3:pembro 200 mg+len 25 mg+dex 20 mg, Part 3:pembro 200 mg+len 25 mg+dex 40 mg |
| CarfilzomibAlso: KYPROLIS®IV infusion | Drug | Part 3:pembro 200 mg+carf 56 mg/m^2+dex 20 mg |
Primary outcome
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
Time frame: Up to 28 days in Cycle 1
DLTs were assessed during Cycle 1 (28 days) and were defined as the occurrence of any of the following judged by the investigator to be possibly, probably or definitely related to study drug: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days; Gr 3 non-hematologic toxicity lasting >3 days; Gr 3 non-hematologic laboratory value if: medical intervention was required, abnormality led to hospitalization, was renal or liver function related, or persisted for >1 week; Gr 3/4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (associated with bleeding requiring platelet transfusion or life-threatening bleeding); Gr 5 toxicity; or delay of >1 week in initiating Cycle 2 or unable to complete 80% of treatment during the first course of therapy due to drug-related toxicity. DLTs for the rMM cohort were any drug-related adverse events that cannot be managed by dose modification. DLTs are reported for the maximum tolerated dose.
Number of Participants Who Experienced One or More Adverse Events (AEs)
Time frame: Up to approximately 72.7 months
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time frame: Up to approximately 72.7 months
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.
2 secondary outcomes
Objective Response Rate (ORR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
Time frame: Up to approximately 72.7 months
Disease Control Rate (DCR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
Time frame: Up to approximately 72.7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31090915Mateos MV, Orlowski RZ, Ocio EM, Rodriguez-Otero P, Reece D, Moreau P, Munshi N, Avigan DE, Siegel DS, Ghori R, Farooqui MZH, Marinello P, San-Miguel J. Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol. 2019 Sep;186(5):e117-e121. doi: 10.1111/bjh.15946. Epub 2019 May 15. No abstract available.
- Merck Oncology Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) (time frame: Up to 28 days in Cycle 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02036502, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.