Interim Results from Phase Ib/II CLASSICAL-Lung Study Show Promise in NSCLC

Updated interim results from CLASSICAL-Lung, a phase Ib/II study of pepinemab in combination with avelumab (Bavencio) showed promise in patients with non-small cell lung cancer (NSCLC), according to a presentation at the American Association for Cancer Research (AACR) Virtual Annual Meeting I, held from April 27-28, 2020.¹

The multi-center, open-label study is designed to evaluate the combination in 62 patients with advanced stage (IIIB/IV) NSCLC, including immunotherapy-naïve patients and those whose tumors progressed during or following chemotherapy.² The data presented at AACR builds upon results previously presented at the 34^th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in November 2019.³

“Pepinemab is a humanized IGG4 antibody which binds to and blocks SEMA4D activity,” Jonathan W. Goldman, MD, from UCLA in Santa Monica, California, said in a poster presentation at the meeting. “Preclinical studies have shown this allows for an enhanced effect of immune checkpoint inhibitor therapies.” 

The study design also included a 12-subject dose escalation phase to determine the recommended phase II dose of pepinemab in combination with avelumab, followed by a 50-subject dose expansion phase. The primary objective of the trial was to assess safety and tolerability, and secondary objectives include evaluation of efficacy, immunogenicity, and PK/PD. An additional exploratory objective is to identify candidate biomarkers of activity. 

Of 29 evaluable IOF patients, 2 experienced confirmed partial response (PR) with 66% and 52% tumor reduction following acquired resistance to prior treatment with pembrolizumab. Moreover, 15 additional patients experienced stable disease (SD), and at least 7 participants had durable clinical benefit of ≥ 23 weeks. Among 21 evaluable ION patients, 5 experienced PR and had clinical benefit ≥ 1 year. 

The disease control rate was found to be 81%. Further, analysis of pre- and on-treatment biopsies demonstrated increased CD8⁺ T-cell density associated with response, with reduction or elimination of tumor in 10 of 11 biopsies from subjects with PR or SD. Notably, 79% of patients who experienced PR or SD were reported to have tumors with negative or low PD-L1 expression. 

“Interestingly, tumor cell density also went down for the patients having a partial response or stable disease, but it is difficult to know what to make of this,” said Goldman.

Enrollment for this trial is complete, and the interim analysis suggests that the combination of pepinemab plus avelumab is well tolerated and shows initial clinical signs of antitumor activity. However, updated clinical response data, as well as immunophenotyping of both inflammatory and suppressive myeloid cells, will be presented at a future date.

References:

1. AACR. CT191 – Interim results from CLASSICAL-Lung, phase 1b/2 study of pepinemab (VX15/2503) in combination with avelumab in advanced NSCLC. AACR website. Published April 27, 2020. aacr20.onlineeventpro.freeman.com/posters/24211315/Interim-results-from-CLASSICAL-Lung-phase-1b2-study-of-pepinemab-VX152503-in-combination-with-avelumab-in-advanced-NSCLC. Accessed April 27, 2020. 

2. AACR. CT191 – Interim results from CLASSICAL-Lung, phase 1b/2 study of pepinemab (VX15/2503) in combination with avelumab in advanced NSCLC. AACR website. Published April 27, 2020. abstractsonline.com/pp8/#!/9045/presentation/10692. Accessed April 27, 2020. 

3. Updated Interim Results from CLASSICAL-Lung, Phase Ib/II Study of Pepinemab (VX15/2503) in Combination with Avelumab (Bavencio) in Non-Small Cell Lung Cancer Presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting [news release]. Rochester, NY. Published April 27, 2020. ir.vaccinex.com/news-releases/news-release-details/updated-interim-results-classical-lung-phase-1b2-study-pepinemab. Accessed April 27, 2020.