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A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: SAR650984 (SAR) is a naked humanized IgG1 monoclonal antibody that binds to the CD38 receptor. SAR kills tumor cells via ADCC, CDC, direct apoptosis without secondary crosslinking and allosteric inhibition on CD38 enzymatic activity. Data on relapsed /refractory multiple myeloma (RRMM) patients (pts) in the dose escalation phase of the study are reported. (NCT01084252). Methods: SAR was given IV weekly (QW) or every 2 weeks (Q2W). Dose levels (DL) 0.3, 1, 3, 5, 10 and 20 mg/kg Q2W and 10 mg/kg QW using the classic 3+3 design were evaluated. Results: 35 pts with RRMM were treated; median age 64 yrs (40-76); median lines of therapy were 6 (2-14), 34/35 received an IMiD and a proteasome inhibitor (57% had carfilzomib (C) and/or pomalidomide (P). MTD was not reached at any DL. Adverse events in ≥ 10% of pts at all DL, regardless of causality, were fatigue (48.6%), nausea (34.3%), pyrexia (28.6%), anemia (28.6%), cough (25.7%), headache (25.7%), upper respiratory infection and chills (22.9%), dyspnea (20%), constipation (17.1%), diarrhea and vomiting (14.3%) and bone pain, chest discomfort, muscle spasms, thrombocytopenia and hypokalemia in 11.4% of pts. SAR related ≥ G 3 adverse events included pneumonia (n = 3), with hyperglycemia, hypophosphatemia, pyrexia, apnea, fatigue, thrombocytopenia and lymphopenia in 1 pt each. Investigator assessment by EBMT response criteria (ORR ≥ PR) among 34 evaluable pts was 24% (CR n = 2, PR n = 6). Responses occurred at all DL ≥ 1 mg/kg. Clinical benefit response (≥ MR) was 29% with 41% SD. In the ≥10 mg/kg cohort ORR was 33% (n =6/18) and CBR was 39% (n =7/18). The time to response was 4.6 weeks and time on treatment was 9.9 weeks (2-81). 10 pts remain on treatment. The expansion cohort dose was selected based on efficacy, safety, and receptor occupancy data. Conclusions: The MTD of SAR was not reached. SAR demonstrates encouraging and durable single agent efficacy in heavily pretreated RRMM pts, including those with prior (C) and (P) and warrants further evaluation. Clinical trial information: NCT01084252.
|Response EBMT *||All DL
|ORR||(8) 24%||(6) 33%|
|CBR||(10) 29%||(7) 39%|
|PD||(10) 29%||(4) 22%|
|MR||(2) 6%||(1) 5%|
|PR||(6) 18%||(4) 22%|
|CR||(2) 6%||(2) 11%|
*Investigator assessment of response as of Dec 31, 2013.
Abstracts by Thomas G. Martin:
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Presentations by Thomas G. Martin:
A Phase Ib Dose-Escalation Trial of SAR650984 (Anti-CD38 mAb) in Combination with Lenalidomide and Dexamethasone in Relapsed/Refractory Multiple MyelomaMeeting: 2014 ASCO Annual Meeting Abstract No: 8512Session: Myeloma (Oral Abstract Session)