MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma (MEDI2228)

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

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.

Study Overview

• Status: Completed
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Biological: Dose Escalation, MEDI2228, ADC (antibody drug conjugate); Biological: Dose Expansion, MEDI2228, ADC (antibody drug conjugate)

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • Research Site
• Greece
  • Athens, Greece, 11528
    • Research Site
• Spain
  • Badalona, Spain, 08916
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 101 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be ≥ 18 years of age at the time of screening.

2. 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:

   1. Serum M-protein ≥ 0.5 g/dL
   2. Urine M-protein ≥ 200 mg/24 hours
   3. Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal.
3. Subjects must either be ineligible for or post-autologous stem cell transplant.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
5. 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:

1. 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
2. Subjects who have previously received an allogeneic stem cell transplant
3. Central nervous system (CNS) involvement(including meningeal involvement) by MRI or cerebrospinal fluid exam

4. 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:

5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Escalation, MEDI2228, ADC; 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); 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
EXPERIMENTAL: Dose Expansion, MEDI2228, ADC; 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2018
• Primary Completion (ACTUAL): March 21, 2022
• Study Completion (ACTUAL): March 21, 2022

Study Registration Dates

• First Submitted: March 17, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (ACTUAL): April 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: open-label; multiple myeloma; relapsed/refractory
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoconjugates
• Other Study ID Numbers: D7900C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca/MedImmune group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca/MedImmune will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca/MedImmune will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No