MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma

Phase 1

Completed

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

• Registration Number: NCT03489525
• Lead Sponsor: MedImmune LLC

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-17
• Study First Submitted QC: 2018-03-29
• Study First Posted: 2018-04-05
• Study Start: 2018-05-08
• Status Verified: 2022-03
• Primary Completion: 2022-03-21
• Study Completion: 2022-03-21
• Last Update Submitted: 2022-03-25
• Last Update Posted: 2022-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation, MEDI2228, ADC	Dose Escalation, MEDI2228, ADC (antibody drug conjugate)	Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with relapsed/refractory (R/R) multiple myeloma (MM).
Dose Expansion, MEDI2228, ADC	Dose Expansion, MEDI2228, ADC (antibody drug conjugate)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Research Site; 🇪🇸 Badalona, Spain