MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, pharmacokinetics and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI2228 in adult subjects with multiple myeloma who are either transplant ineligible or post autologous stem cell transplant and are relapsed/refractory.

Official Title
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A Phase 1, Open-label Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: Dose Escalation, MEDI2228, ADC (antibody drug conjugate)
* Biological: Dose Expansion, MEDI2228, ADC (antibody drug conjugate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be ≥ 18 years of age at the time of screening. Subjects must have a confirmed diagnosis of relapsed/refractory MM as per IMWG criteria (Rajkumar et al, 2014) and have exhausted standard of care regimens with proven clinical benefit, which include agents from the following anti myeloma therapies: PIs, IMIDs, and mAbs and have measurable disease with at least one of the following criteria: Serum M-protein ≥ 0.5 g/dL Urine M-protein ≥ 200 mg/24 hours Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal. Subjects must either be ineligible for or post-autologous stem cell transplant. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Adequate organ and marrow functions as determined per protocol-defined criteria. Exclusion Criteria Any of the following would exclude the subject from participation in the study: Target Disease: Subjects who have previously received an autologous stem cell transplant if less than 90 days have elapsed from the time of transplant or the subject has not recovered from transplant associated toxicities prior to the first scheduled dose of MEDI2228 Subjects who have previously received an allogeneic stem cell transplant Central nervous system (CNS) involvement(including meningeal involvement) by MRI or cerebrospinal fluid exam Known history of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, plasma cell leukemia, Waldenstrom's macroglobulinemia, or amyloidosis Medical History and Concurrent Diseases: Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 101 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation, MEDI2228, ADC<br>Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with relapsed/refractory (R/R) multiple myeloma (MM). | Biological: Dose Escalation, MEDI2228, ADC (antibody drug conjugate)<br>* Single agent MEDI2228 will be administered to adult subjects with R/R MM. The study aims to evaluate up to 9 planned, sequentially ascending main dose levels<br>|
| Experimental: Dose Expansion, MEDI2228, ADC<br>Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with R/R MM in the dose-expansion cohort at the dose selected for evaluation in the dose-expansion phase. | Biological: Dose Expansion, MEDI2228, ADC (antibody drug conjugate)<br>* Adult subjects with R/R MM with measurable disease will be enrolled in the dose-expansion cohort at the dose selected for evaluation in the dose-expansion phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events (AEs) | To assess by the occurrence of adverse events (AEs) | From time of informed consent through 90 days post end of treatment | 
| Occurrence of SAE (serious adverse events) | To assess the occurrence of serious adverse events (SAEs) | From time of informed consent through 90 days post end of treatment | 
| Occurrence of DLTs (dose limiting toxicities) | To assess by the occurrence of hematologic and non-hematologic toxicities, AEs, and abnormal laboratory results | From time of informed consent through 90 days post end of treatment | 
| Number of patients with changes in laboratory parameters from baseline | To assess serum chemistry, hematology, coagulation and urninalysis | From time of informed consent and up to 21 days post end of treatment | 
| Number of patients with changes in vital signs from baseline | To assess body temperature, blood pressure and heart rate | From time of informed consent and up to 21 days post end of treatment | 
| Number of patients with changes in elctrocardiogram (ECG) results from baseline | To assess using 12 lead ECG recordings | From time of informed consent and up to 21 days post end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MEDI2228 maximum observed concentration for PK | To assess the pharmacokinetics of MEDI2228 | From time of informed consent through 60 days post end of treatment | 
| MEDI2228 area under the concentration-time curve for PK | To assess the pharmacokinetics of MEDI2228 | From time of informed consent through 60 days post end of treatment | 
| MEDI2228 clearance for PK | To assess the pharmacokinetics of Medi2228 | From time of informed consent through 60 days post end of treatment | 
| MEDI2228 terminal half-life for PK | To assess the pharmacokinetics of MEDI2228 | From time of informed consent through 60 days post end of treatment | 
| Number of subjects who develop anti-drug antibodies (ADAs) | To assess immunogenicity of MEDI2228 | From time of informed consents through 60 days post end of treatment | 
| Objective response rate (ORR) | To assess the anti-tumor activity of MEDI2228 | From time of informed consent and up to three years after final patient is enrolled | 
| Clinical benefit rate | To assess clinical benefit of MEDI2228 | From time of informed consent up to three years after final patient is enrolled | 
| Duration of response (DoR) | To assess the anti-tumor activity of MEDI2228 | From time of informed consent and up to three years after final patient is enrolled | 
| Progression free survival (PFS) | To assess the anti-tumor activity of MEDI2228 | From time of informed consent and up to three years after final patient is enrolled | 
| Overall Survival (OS) | To assess the anti-tumor activity of MEDI2228 | From time of informed consent and up to three years after final patient is enrolled | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple myeloma, relapsed/refractory, open-label