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.

SparkCures ID 951
Trial Phase Phase 1
Enrollment 142 Patients
Trial Sponsors
  • MedImmune
NCT Identifier


Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

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

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Mayo Clinic Hospital

Phoenix, AZ

Mayo Clinic (Jacksonville)

Jacksonville, FL

Mayo Clinic (Rochester)

Rochester, MN

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Mayo Clinic Hospital

Phoenix, AZ

Mayo Clinic (Jacksonville)

Jacksonville, FL

Mayo Clinic (Rochester)

Rochester, MN

North Carolina

Published Results

Phase 1, First-in-Human Study of MEDI2228, a BCMA-Targeted ADC in Patients with Relapsed/Refractory Multiple Myeloma

December 02, 2020

As of May 15, 2020, 82 pts received MEDI2228 during dose escalation and expansion. All pts had received prior therapy with an IMiD, PI, and mAb: lenalidomide, 76 (94%); pomalidomide, 68 (84%); bortezomib, 77 (95%); carfilzomib, 64 (79%); and daratumumab, 71 (87%). Pts received between 2–11 lines of prior regimens. At 0.2 mg/kg, 2 pts experienced DLTs (grade 3/4 thrombocytopenia) without bleeding; no DLTs were reported for other dose levels. The maximum tolerated dose was 0.14 mg/kg Q3W. Treatment-related adverse events (TEAEs) occurring in ≥20% of pts in the 0.14 mg/kg cohort were photophobia (53.7%), thrombocytopenia (31.7%), rash (29.3%), increased gamma-glutamyltransferase (24.4%), dry eye (19.5%), and pleural effusion (19.5%). No reports of keratopathy or visual acuity loss were observed in the 0.14 mg/kg cohort. The TEAE profiles at lower-dose levels were similar but with lower incidences compared with the 0.14 mg/kg level. Efficacy was demonstrated at all dose levels (dose, objective response rate [ORR], [n]): 0.0125 mg/kg, 33.3% [1/3]; 0.025 mg/kg, 16.7% [1/6]; 0.05 mg/kg, 33.3% [3/9]; 0.10 mg/kg, 27.8% [5/18]; 0.14 mg/kg, 61.0% [25/41]; 0.2 mg/kg, 40.0%, [2/5]. In the 0.14 mg/kg cohort, ORR was 61.0% (95% confidence interval [CI]: 44.5%, 75.8%); there were 10 (24.4%) very good partial responses (VGPRs), 15 (36.6%) partial responses, and 3 (7.3%) minimal responses. Four of the VGPR pts were immunofixation negative. Most (90.2%) pts in the 0.14 mg/kg cohort had received prior daratumumab. Median duration of response (DOR) in the 0.14 mg/kg cohort was not reached. MEDI2228 exhibited linear PK at doses of ≥0.05 mg/kg Q3W that was minimally impacted by circulating levels of soluble BCMA at baseline. There was no difference in BCMA expression by IHC in the bone marrow of responders compared with nonresponders. Thirty-six pts in the 0.14 mg/kg cohort discontinued treatment due to adverse events (n=24), progressive disease (n=8), patient decision (n=2), investigator decision (n=1), or death (n=1).


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