1521P - Addition of durvalumab to CROSS in oesophageal adenocarcinoma is feasible and safe

Background

Anti-PD-(L)1 is effective in esophago-gastric adenocarcinoma (EGA) and appears synergistic with chemoradiotherapy (CRT). The RICE trial aims to evaluate safety, feasibility and efficacy of addition of neoadjuvant durvalumab and adjuvant durvalumab ± tremelimumab to standard CRT.

Methods

In this open-label, randomized phase-2 trial, pts with locally advanced (≥uT3/Nx or uT2/N+) non-metastatic EGA (including EGJ-I and EGJ-II) receive two doses of neoadjuvant durvalumab (1500mg) in addition to CRT according to the CROSS protocol. After a safety-run in of 6 pts, adjuvant therapy was randomized 1:1 to 12 doses of durvalumab monotherapy or 12 doses of durvalumab (1500mg/4w) plus a single dose of adjuvant tremelimumab (300mg d1 of adjuvant treatment). Here we report the results from the neoadjuvant part of the trial including the primary endpoints for safety and efficacy and extensive translational immune monitoring.

Results

In the modified intention to treat analyses 95% (53/56) of pts completed neoadjuvant therapy and 93% (52/56) underwent resection (3 excluded due to peritoneal carcinomatosis, 1 to intraoperatively identified cirrhosis; R0 in all pts), which was not lower than 90.4% as predefined benchmark for feasibility. Regarding the primary endpoints for safety, the rate of anastomotic leakage was 6% (3/52) and significantly lower than the predefined threshold of 22% (p<0.05), while the rate of grade 3/4 toxicity exceeded the predefined threshold of 13% (25%, 13/56 G3, 1/56 G4). Clinicopathological evaluation of response revealed 5% (3/56) peritoneal carcinomatosis, 39% (22/56) minor response (>10% vital tumor), 30% (17/56) major response (<10%), 23% (13/56) complete response and 2% not evaluable (1/56, cirrhosis).The primary endpoint for efficacy (35% CR) was not reached, but at least <10% residual tumour was achieved in 53%, which was higher than in patients treated with CROSS during the same period at the same center (38.6%; 56/145; p<0.05). Patterns of response and resistance from translational analyses will be presented as well.

Conclusions

The first analyses of the RICE trial demonstrate safety and feasibility of addition of neoadjuvant immunotherapy with durvalumab to CROSS.

Clinical trial identification

NCT04159974.

Editorial acknowledgement

Legal entity responsible for the study

University of Cologne.

Funding

AstraZeneca.

Disclosure

H. Schloesser: Non-Financial Interests, Institutional, Research Funding: Tabby Therapeutics, AstraZeneca; Non-Financial Interests, Personal, Advisory Role: BMS. M. von Bergwelt: Non-Financial Interests, Personal, Advisory Board: Tabby Therapeutics. M.J. Hallek: Non-Financial Interests, Personal and Institutional, Advisory Board: Roche, Gilead Sciences, AbbVie, AstraZeneca, Janssen. T. Zander: Non-Financial Interests, Institutional, Research Funding: AstraZeneca; Non-Financial Interests, Personal and Institutional, Advisory Board: BMS, MSD. All other authors have declared no conflicts of interest.