A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, Plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers.

Abstract

Purpose: Neoadjuvant chemoradiation (NCRT) followed by surgical resection represents a standard approach for patients with locally advanced esophageal/GEJ cancers. Sotigalimab is a high affinity CD40 agonist antibody capable of inducing and expanding anti-tumor immune responses by activating dendritic cells, T and B lymphocytes, NK cells, and M1 macrophages. This study examined the safety and efficacy of combining sotigalimab with NCRT in patients with esophageal or GEJ cancers.

Patients and methods: Patients with resectable (T1-3, Nx) adenocarcinoma(AC) or squamous cell carcinoma(SCC) of the esophagus or GEJ were eligible. T1N0 and cervical tumors were excluded. Study treatment: weekly carboplatin/paclitaxel with concurrent radiation 5040 cGy plus 3-4 doses of sotigalimab prior to Ivor-Lewis esophagectomy. Primary efficacy endpoint was pathologic complete response (path CR) rate.

Results: 33 patients were enrolled (AC 76%, SCC 24%; clinical stage III 67%). Ninety percent of patients received all planned doses of sotigalimab. The most common adverse events attributed to sotigalimab were nausea, fever/chills, fatigue, and cytokine release syndrome (CRS); most of these were Grade 1-2. Grade >3 CRS was observed in 3 pts (9%). Twenty-five of the 29 efficacy-evaluable patients underwent an R0 resection (87.9%), with an overall path CR rate of 37.9% (11/29). Post-tumor samples demonstrated increased infiltration and activation of dendritic cells, monocytes, and cytotoxic T cells compared to baseline.

Conclusions: Sotigalimab combined with NCRT for esophageal or GEJ cancers was generally well tolerated and achieved path CR rates that compare favorably to historical data and are promising for this treatment strategy.

Clinical trial information: NCT03165994.