Interim results from the CLASSICAL-Lung phase Ib/II clinical trial of pepinemab, an IgG4 humanized monoclonal antibody targeting semaphorin 4D, in combination with the anti–programmed cell death ligand 1 antibody avelumab for patients with advanced NSCLC showed that the treatment is well tolerated and has initial clinical signals of antitumor activity. The study by Shafique et al will be presented during the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium (Abstract 75).
With the exception of nonmelanoma skin cancer, lung cancer is the most commonly diagnosed cancer worldwide and is the leading cause of cancer-related death in the United States and worldwide. Despite research advances in immune checkpoint inhibitors in the treatment of NSCLC, many patients with the cancer are refractory to or acquire resistance to current therapies, necessitating rational combination therapies to overcome resistance mechanisms in the disease.
CLASSICAL-Lung
The ongoing CLASSICAL-Lung clinical trial is investigating the combination of pepinemab with avelumab to couple beneficial modifications of the immune microenvironment via pepinemab with immune activation via checkpoint inhibition. The study is evaluating the safety, tolerability, and efficacy of this combination treatment in patients with stage IIIB/IV NSCLC, including immunotherapy-naive patients and patients whose tumors progressed during or following immunotherapy.
KEY POINTS
- Among 29 patients whose tumors had progressed during or following immunotherapy, 2 experienced confirmed partial response, with 63% and 52% tumor reduction on the study following acquired resistance to prior treatment with pembrolizumab; 15 patients experienced stable disease; and at least 5 patients experienced durable clinical benefit of ≥ 23 weeks.
- Among 21 immunotherapy-naive patients, 5 experienced a partial response, clinical benefit ≥ 1 year was observed in 3 patients, and the disease control rate was 81%.
Study Results
The researchers found that this treatment combination was well tolerated and no major safety signals were identified. Among 29 evaluable patients whose disease progressed during or following prior treatment with immunotherapy, 2 had a confirmed partial response, with 63% and 52% tumor reduction on the study following acquired resistance to prior treatment with pembrolizumab; 15 additional patients experienced stable disease; and at least 5 patients experienced durable clinical benefit of ≥ 23 weeks. Among 21 evaluable immunotherapy-naive patients, 5 had a partial response, clinical benefit ≥ 1 year was observed in 3 patients, and the disease control rate was 81%. Analysis of pre- and on-treatment biopsies demonstrated increased CD8-positive T-cell density correlating with response, reduction, or elimination of the tumor in 11 of 13 biopsies from patients with a partial response or stable disease.
“Interim analysis suggests the combination of pepinemab plus avelumab is well tolerated and shows initial clinical signals of antitumor activity. Updated clinical response data (minimum of 6 months follow-up), as well as additional immunophenotyping of both inflammatory and suppressive myeloid cells, will be presented.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
