MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma

Relapsed/Refractory Multiple Myeloma Clinical Trial

— MEDI2228  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03489525
• Other study ID #: D7900C00001
• Status: Completed
• Phase: Phase 1
• Start date: May 8, 2018
• Est. completion date: March 21, 2022

Study information

• Verified date: March 2022
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: March 21, 2022
• Est. primary completion date: March 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

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
• 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.

Locations

Country	Name	City	State
Australia	Research Site	Melbourne
Greece	Research Site	Athens
Spain	Research Site	Badalona
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Detroit	Michigan
United States	Research Site	Fairfax	Virginia
United States	Research Site	Jacksonville	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Australia,  Greece,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	MEDI2228 maximum observed concentration for PK	To assess the pharmacokinetics of MEDI2228	From time of informed consent through 60 days post end of treatment
Secondary	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
Secondary	MEDI2228 clearance for PK	To assess the pharmacokinetics of Medi2228	From time of informed consent through 60 days post end of treatment
Secondary	MEDI2228 terminal half-life for PK	To assess the pharmacokinetics of MEDI2228	From time of informed consent through 60 days post end of treatment
Secondary	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
Secondary	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
Secondary	Clinical benefit rate	To assess clinical benefit of MEDI2228	From time of informed consent up to three years after final patient is enrolled
Secondary	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
Secondary	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
Secondary	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