A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies

Study Overview
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Brief Summary
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To assess safety and tolerability, describe the dose-limiting toxicities, determine the maximum tolerated dose (MTD) or the highest protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and a recommended dose for further evaluation of MEDI7247 in patients with selected hematological malignancies who have relapsed after, or are refractory to prior standard therapy, and for whom there is no standard salvage regimen available.

Official Title
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A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies

Conditions
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Acute Myeloid Leukemia, Multiple Myeloma, Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: MEDI7247


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available. Age ≥ 18 years at the time of screening. Written informed consent and any locally required authorization Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Liver Function Tests: AST and ALT ≤ 3 × ULN, and serum TBL ≤ 1.5 × ULN, unless consistent with Gilbert's syndrome for which TBL ≤ 2.5 × ULN is allowed. 5. CrCL ≥ 40 mL/min 6. Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from 7 days post-screening, and must agree to continue using such precautions for 90 days after the last dose of investigational product. 7. Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product. Exclusion Criteria: Received cytotoxic chemotherapy within 21 days (or 42 days for nitrosureas or mitomycin C) prior to the first scheduled dose of MEDI7247. Received major surgery (as defined by the Investigator), radiotherapy, or immunotherapy (including immune checkpoint inhibitors and adoptive cellular therapy such as autologous or donor NK cell or T lymphocyte infusions (e.g. CAR -T cells)) within 28 days of the first scheduled dose of MEDI7247. Received an investigational drug within 14 days of the first scheduled dose of MEDI7247 or not recovered from associated toxicities. Patients who have previously received an autologous SCT, are excluded if less than 120 days have elapsed from the time of transplant or the patient has not recovered from transplant-associated toxicities prior to the first scheduled dose of MEDI7247. History of liver cirrhosis, liver fibrosis or prior liver irradiation regardless of the time interval (not including total body irradiation administered during allogeneic SCT). Failure to recover from all prior treatment-related non-hematological toxicities to ≤ Grade 1 prior to the first scheduled dose of MEDI7247 (except for alopecia and neuropathy). Patients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days). Current severe active systemic disease including active concurrent malignancy Central nervous system (CNS) disease that is untreated, symptomatic, or requires therapy to control symptoms. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acute myeloid leukemia<br>Patients with R/R AML by World Health Organization (WHO) classification (Arber et al, 2016) who have failed prior standard therapy and for whom no standard therapies are available | Drug: MEDI7247<br>* The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV<br>|
| Experimental: Multiple Myeloma<br>Patients with R/R MM who have failed prior standard therapy(ies) which should include immunomodulatory agents and proteasome inhibitors and for whom there is no standard salvage regimen. | Drug: MEDI7247<br>* The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV<br>|
| Experimental: Diffuse Large B-cell Lymphoma<br>Patients with R/R DLBCL who have failed prior standard therapy(ies) and for whom there is no standard salvage regimen. | Drug: MEDI7247<br>* The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV<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 serious adverse events (SAEs) | To assess by the occurrence of serious adverse events (SAEs) | From time of informed consent through 90 days post end of treatment | 
| Occurrence of dose-limiting toxicities (DLTs) | To assess by the occurrence of non-Hematologic and hematologic toxicities, AEs, and abnormal laboratory results. | During the evaluation period of 21 or 42 days post-first dose | 
| Number of patients with changes in laboratory parameters from baseline | To assess serum chemistry, hematology, Coagulation and urinalysis | 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 electrocardiogram (ECG) results from baseline | To assess using twelve-lead ECG recordings | From time of informed consent and up to 21 days post end of treatment | 
| Percentage of patients with changes in laboratory parameters from baseline | To assess serum chemistry, hematology, Coagulation and urinalysis | From time of informed consent and up to 21 days post end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MEDI7247 maximum observed concentration for PK | To assess the Pharmacokinetics of MEDI7247 | From time of informed consent through 30 days post end of treatment | 
| MEDI7247 area under the concentration-time curve for PK | To assess the Pharmacokinetics of MEDI7247 | From time of informed consent through 30 days post end of treatment | 
| MEDI7247 clearance for PK | To assess the Pharmacokinetics of MEDI7247 | From time of informed consent through 30 days post end of treatment | 
| MEDI7247 terminal half-life for PK | To assess the Pharmacokinetics of MEDI7247 | From time of informed consent through 30 days post end of treatment | 
| Number of subjects who develop anti-drug antibodies (ADAs) | To assess the immunogenicity of MEDI7247 | From time of informed consent through 30 days post end of treatment | 
| Best overall response (BOR) | To assess the anti-tumor activity of MEDI7247 | From time of informed consent and up to 3 years after final patient is enrolled | 
| Objective response rate (ORR) | To assess the anti-tumor activity of MEDI7247 | From time of informed consent and up to 3 years after final patient is enrolled | 
| Time to response (TTR) | To assess the anti-tumor activity of MEDI7247 | From time of informed consent and up to 3 years after final patient is enrolled | 
| Duration of response (DoR) | To assess the anti-tumor activity of MEDI7247 | From time of informed consent and up to 3 years after final patient is enrolled | 
| Progression-free survival (PFS) | To assess the anti-tumor activity of MEDI7247 | From time of informed consent and up to 3 years after final patient is enrolled | 
| Overall survival (OS) | To assess the anti-tumor activity of MEDI7247 | From time of informed consent and up to 3 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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AML, MEDI7247, Acute Myeloid Leukemia, Multiple Myeloma, Diffuse Large B-cell Lymphoma, MM, DLBCL