5403 - Interim analysis of a phase II trial of perioperative chemotherapy plus avelumab in esophagogastric and gastric adenocarcinoma

Background

Perioperative chemotherapy improves cure rate in locally advanced esophagogastric and gastric adenocarcinoma. Immunotherapy is active at the metastatic stage. Our hypothesis is that the addition of avelumab, an anti-PD-L1 antibody, to perioperative chemotherapy, will increase pathologic complete response (pCR), a potential surrogate for overall survival, compared to historical controls.

Methods

Single-arm phase II study of avelumab + chemotherapy (modified DCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: gastric or gastro-esophageal adenocarcinoma, locally advanced disease, adequate organ function, performance status 0-1, stages Ib, II and III. Main exclusion criteria: other histologies, metastatic disease, use of immunosuppressants, serious autoimmune disease, daily intake of more than 10 mg of prednisone (or equivalent). Statistical hypothesis: this experimental regimen will result in a 20% pCR rate compared to 7% observed with chemotherapy alone. Optimal Simon 2-stage design: if less than 2 pCR/near-pCR are identified in the first 16 cases, the study will be closed for futility. The experimental regimen will be considered for further study if at least 6 pCR are identified in 50 operated patients. Adverse effects are prospectively recorded according to CTCAE guidelines.

Results

From February 2018 to March 2019, 18 patients have been enrolled. Two withdrew consent after starting treatment. Of 16 active patients, 14 were staged as cT3, and 12 as cN+. Thirteen have been operated to date, none having shown radiologic or PET progression. All resections are R0. Eight patients have pN0 status. Two have shown near-pCR (tumor regression score 1). There is one instance of grade 4 hematological toxicity (neutropenia without fever). Grade 3-4 nonhematological toxicity consists of: stomatitis, nausea, diarrhea, all in one patient; arthralgia in one patient; aspiration pneumonia (esophageal obstruction) and postoperative pneumonia, one patient each.

Conclusions

Our findings indicate encouraging safety and activity of avelumab + mDCF as a perioperative regimen. Complete interim analysis results will be presented at the meeting.

Clinical trial identification

NCT03288350.

Editorial acknowledgement

Legal entity responsible for the study

Research Institute of McGill University Health Centre.

Funding

EMD Serono, Research Institute of McGill University Health Centre.

Disclosure

T. Alcindor: Research grant / Funding (self): EMD Serono; Advisory / Consultancy: Astellas; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Taiho; Advisory / Consultancy: Shire; Advisory / Consultancy: BMS. All other authors have declared no conflicts of interest.