Non-Small Cell Lung Cancer Coverage from Every Angle

ASCO–SITC 2020: Interim Trial Results With Pepinemab/Avelumab in Advanced NSCLC

By: Celeste L. Dixon
Posted: Friday, February 14, 2020

Interim trial results showed that pepinemab, a first-in-class humanized monoclonal antibody targeting semaphorin 4D (SEMA4D), in combination with the anti–PD-L1 antibody avelumab produced antitumor activity in patients with non–small cell lung cancer (NSCLC). Blocking SEMA4D may overcome resistance mechanisms of immune exclusion and myeloid suppression, proposed Michael Rahman Shafique, MD, of Moffitt Cancer Center and Research Institute in Tampa, and colleagues. These early-phase study findings were presented at the 2020 American Society of Clinical Oncology–Society for Immunotherapy of Cancer (ASCO-SITC) Clinical Immuno-Oncology Symposium in Orlando (Abstract 75).

In the ongoing phase Ib/II CLASSICAL-Lung trial, pepinemab is given in combination with the avelumab to patients with stage IIIB/IV NSCLC “to couple beneficial modifications of the immune microenvironment with immune activation via checkpoint inhibition,” noted the authors. The evaluable cohort included immunotherapy-naive patients (n = 21) and those whose tumors progressed during or after immunotherapy (n = 29).

In addition to being generally well tolerated, the combination was associated in the prior-immunotherapy arm with 2 confirmed partial responses, 15 additional cases of stable disease, and 5 patients with a durable clinical benefit of 23 or more weeks. Among the immunotherapy-naive patients, five experienced a partial response, and three had a clinical benefit of 1 year or more.

In 11 of 13 biopsies of patients who showed a partial response or stable disease, CD8-positive T-cell density was increased. Preclinical models had shown that combinations of anti-SEMA4D agents with various immunotherapies enhanced T-cell infiltration and activity, as well as durable tumor regression, noted Dr. Shafique and co-investigators.

Disclosure: For full disclosures of the study authors, visit

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