1454GCC: Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is an open label trial of Anti PD1/MD-3475, Pomalidomide and dexamethasone. The study will use standard (FDA approved) doses for both pomalidomide and dexamethasone. The experimental drug Anti PD-1 (MK 3475) given on days 1 and 14.

Detailed Description
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This phase I/II study is focused on patients with relapsed or refractory multiple myeloma. MK-3475 will be given as an intravenous infusion at every 2 weeks. Treatment will be administered on an outpatient basis.

Official Title
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1454GCC: Phase I/II Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: MK-3475
* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of relapsed and/or refractory MM according to International Myeloma Working Group guidelines (2003) Received two lines of prior therapy that includes an IMiD (lenalidomide or thalidomide) and a proteasome inhibitor (bortezomib and/or carfilzomib) (used either separately or in combination). (a). Prior pomalidomide therapy is permitted, provided the patient achieved at least a partial remission and had not progressed for 3 months after stopping therapy. Measureable disease as defined by the protocol (assessed within 28 days prior to registration). Be willing and able to provide written informed consent/assent for the trial. Be over 18 years of age on day of signing informed consent. Have a performance status of 2 on the ECOG Performance Scale. Demonstrate adequate organ function as defined by the protocol. Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study drug. Male subjects should agree to use an adequate method of contraception. Exclusion Criteria: Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. Has a diagnosis of immunodeficiency (HIV) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.) Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or situ cervical cancer that has undergone potentially curative therapy. Has known active central nervous system disease and/or carcinomatous meningitis. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Has evidence of interstitial lung disease or active, non-infectious pneumonitis. Has an active infection requiring systemic therapy. Has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Pregnant or breastfeeding, or expecting to conceive or father children during study participation. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as per the protocol. has known active Hepatitis B or Hepatitis C. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomalidomide, Dexamethasone & MK-3475<br>Pomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). | Drug: MK-3475<br>* Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks.<br>* Other names: Generic name: Pembrolizumab - Trade name: Keytruda;Drug: Pomalidomide<br>* Pomalidomide is given at standard dose of 4 mg daily orally for 21 days<br>* Other names: Pomalyst, CC-4047, Actimid;Drug: Dexamethasone<br>* Dexamethasone is given at 40 mg orally weekly<br>* Other names: Decadron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Adverse Events | Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475 | 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD-LI Expression On Myeloma Cells | The identification of a biomarker for response by evaluating PD-1/PDL-1 expression in patients' bone marrow aspirate samples will be analyzed in order to help select patients for future anti-PD-1 therapy. The main exploratory biomarker analysis was to examine potential correlation between expression of PD-1 on T cells and PD-L1 on myeloma cells with clinical outcome using the following parameters: response rate focusing on responses ≥ very good partial response (VGPR) and PFS. SAS software (v.9.4; SAS Institute, Inc, Cary, NC) was used for statistical analyses. | Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months) | 
| Time to Progression Free Survival (PFS) | PFS will be measured in all participants. Survival and PFS functions were estimated using the Kaplan-Meier method. The Cox regression model was used to assess the following plausible risk factors for OS and PFS: age, isotype, number of cycles of therapy, and cytogenetic profile. | PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory, MK-3475 & Pomalidomide, Immunotherapy