The combination of an anti-LAG3 or anti-TIGIT monoclonal antibody with pomalidomide and dexamethasone resulted in promising antitumor activity among patients with relapsed/refractory multiple myeloma (MM) in a phase 1/2 study.
“These data provide the first evidence of clinical activity of TIGIT and LAG-3 blockade in MM,” Hearn J. Cho, Of the Icahn School of Medicine at Mount Sinai, New York, NY concluded in a poster presented at the AACR Annual Meeting 2023.
The platform, phase 1/2 MyCheckpoint trial (ClinicalTrials.gov Identifier: NCT04150965) enrolled patients with MM who had received at least 3 prior lines of therapy, including a proteosome inhibitor, immunomodulatory drug, and an anti-CD38 antibody. There were 14 patients randomly assigned to receive an anti-LAG-3 or anti-TIGIT therapy. All patients received a single cycle of the investigational agent alone, then pomalidomide plus dexamethasone were included beginning with cycle 2.
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At screening, the beginning of cycles 2 and 3, and at the end of the study, bone marrow aspirates and peripheral blood were collected for correlative analyses. The primary objective was to evaluate the safety and overall response rates (ORR) of investigational agents withy pomalidomide and dexamethasone.
The ORR was 28.6% in the anti-LAG-3 cohort, which included 1 very good partial response (VGPR). The disease control rate (DCR) was 85.7%. In the anti-TIGIT cohort, the ORR was 50.0%, which included 2 VGPRs, and a DCR of 100%.
Serial analyses with mass cytometry indicated that treatment with either the anti-LAG-3 or anti-TIGIT antibody and pomalidomide plus dexamethasone caused immune activation.
In the anti-LAG-3 cohort, the most common treatment-related adverse events (TRAEs) of grade 3-4 severity were dyspnea and neutropenia, whereas neutropenia, thrombocytopenia, and anemia were the most common in the anti-TIGIT cohort.
There were no autoimmune events. Considered an event of special interest, 1 patient developed grade 1 aspartate transaminase elevation. There were 2 patients who withdrew from the study due to an adverse event.
Disclosures: This research was supported in part by Bristol-Myers Squibb. Please see the original reference for a full list of disclosures.
Reference
Cho HJ, Richard S, Lesokhin A, et al. Durable responses following anti-TIGIT (BMS-986207) and anti-LAG3 (BMS-980616) in combination with pomalidomide in relapsed myeloma: MMRF MyCheckpoint trial. AACR 2023. April 14-19, 2023. Abstract CT262/2.
