Pepinemab-Bavencio Combo Shows Positive Anti-Tumor Activity in Advanced Lung Cancer, Phase 1/2 Trial Shows

Pepinemab-Bavencio Combo Shows Positive Anti-Tumor Activity in Advanced Lung Cancer, Phase 1/2 Trial Shows

A combination of Vaccinex‘s investigational antibody pepinemab and the immune checkpoint inhibitor Bavencio (avelumab) was well-tolerated and showed signs of lasting anti-tumor activity in patients with advanced non-small cell lung cancer (NSCLC), findings from a Phase 1/2 trial show.

Pepinemab (VX15/2503) is a first-in-class humanized monoclonal antibody being developed for the treatment of different types of cancer. The medication works by targeting a protein called semaphorin 4D (SEMA4D), which behaves abnormally in many types of cancer, contributing to disease progression.

The safety and efficacy of pepinemab in combination with Bavencio, Merck’s immune checkpoint inhibitor, is currently being investigated for patients with advanced NSCLC. A Phase 1b/2 trial (NCT03268057) called CLASSICAL-Lung is being carried out by Vaccinex in collaboration with Merck and Pfizer.

The trial enrolled 62 people with stage III/IV NSCLC who had never been treated with immunotherapy agents, or whose disease had progressed while being treated with immune checkpoint inhibitors.

Interim data from the trial, presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that 63% of eligible patients whose disease had worsened while receiving treatment with a checkpoint inhibitor benefited from the combination therapy, achieving either tumor reduction or stable disease.

“We believe the study’s interim results, although early, are very encouraging, showing that the combination of our lead therapeutic candidate, pepinemab, together with avelumab checkpoint inhibitor, had promising anti-tumor activity in lung cancer patients who were either immunotherapy treatment naïve or had failed prior single agent anti-PD-1/PD-L1 immunotherapy,” Maurice Zauderer, PhD, president and CEO of Vaccinex, said in a press release last year.

“We were also very pleased to see signs of positive changes in the tumor microenvironment that may potentiate the effectiveness of checkpoint therapy. We believe this early data with a 63% positive response suggests synergy between our drug candidate and avelumab in potentially treating certain patients whose tumors progress on approved first or second line immunotherapies,” Zauderer added.

Updated data from CLASSICAL-Lung were presented at the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium, held Feb. 6-8 in Orlando, Fla.

Among the 29 evaluable patients whose disease had progressed while receiving prior treatment, two had partial responses — 63% and 52% tumor reduction — to the combination therapy after acquiring resistance to Keytruda (pembrolizumab), the new data showed.

In this group of patients, 15 achieved a state of stable disease, and at least five had long-lasting clinical benefits lasting at least 23 weeks (nearly six months).

From the 21 eligible patients who had not received prior treatment, five had a partial response and three experienced clinical benefits lasting at least one year. A large proportion of patients — 81% — achieved a complete or partial response, or at least a state of disease stabilization, following treatment with the combo therapy.

Biopsies taken both before and during treatment showed the levels of cancer-fighting immune cells increased over the course of therapy in 11 of the 13 patients who had a partial response to treatment or whose disease stabilized.

Overall, the combination therapy was well-tolerated, raised no major safety concerns, and showed promising anti-tumor properties, the researchers said.