Neoadjuvant nivolumab plus concurrent chemoradiation in stage II/III esophageal/gastroesophageal junction cancer

142 Background: Neoadjuvant chemoradiation (cRT) prior to surgical resection in stage II/III esophageal/gastroesophageal junction (E/GEJ) cancer results in a complete pathologic response rate (pCR) of 20-30%. The appearance of favorable microenvironment features (enhanced tumor infiltrating lymphocytes, perivascular lymphocytes and tertiary lymphoid structures) after induction therapy in resected EC suggest early stage tumors may respond favorably to immune based therapy and in particular to PD-1 blockade when combined with cRT. Methods: In this pilot study, we administered 2 cycles of induction nivolumab (N) q2 weekly prior to standard of care carboplatin/paclitaxel/radiation plus 3 additional cycles of N on week 1, 3 and 5 of cRT. An Ivor-Lewis esophagectomy (E/MIE) was performed 6-10 weeks after the last IO dose. The primary endpoints of the study were safety and feasibility. We also evaluated the pCR, survival and temporal dynamics of T cell receptor clonotypes. Results: Between August 2017 and July 2018, 16 patients were enrolled on study. Induction N and neoadjuvant N combined with cRT in stage II/III E/GEJ cancers has an acceptable toxicity profile and was not associated with delays in surgery. Toxicities of note include steroid responsive grade 3 dermatitis (1/16), grade 3 hepatitis (1/16) and no cases of pneumonitis. To date, 10 patients with E adenocarcinoma have had an E/MIE and the pCR is 4/10 (40%). T cell receptor sequencing of the tumor bed and serial peripheral blood T cells revealed high peripheral representation of tumor-associated T cells. In one notable case, the highest-frequency intratumoral clone decreased in frequency in the peripheral blood upon treatment and rapidly increased after surgical resection, potentially signifying trafficking to the tumor site. Conclusions: Induction N and N combined with cRT has limited side-effects, did not result in surgical delay or enhanced surgical morbidity/mortality and induced a pCR of 40% in stage II/III E/GEJ cancers. Additional efficacy data on the full cohort and more in depth correlative studies will be presented to validate systemic activation of anti-tumor T cell responses. Clinical trial information: NCT03044613.