Abstract 5403
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.
Resources from the same session
4413 - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF trial
Presenter: Ghassan Abou-Alfa
Session: Poster Display session 2
Resources:
Abstract
4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Lorenza Rimassa
Session: Poster Display session 2
Resources:
Abstract
5509 - A Randomized Controlled, Open label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine versus Gemcitabine alone in Patients with Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment (NCT03126435)
Presenter: Li-Tzong Chen
Session: Poster Display session 2
Resources:
Abstract
1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.
Presenter: Sylvie Lorenzen
Session: Poster Display session 2
Resources:
Abstract
2392 - GLOW: Randomized Phase 3 Study of Zolbetuximab + CAPOX Compared With Placebo + CAPOX as First-line Treatment of Patients With CLD18.2⁺/HER2⁻ Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Manish Shah
Session: Poster Display session 2
Resources:
Abstract
5217 - PRODIGE67_UCGI33 ARION: Association of Radiochemotherapy and Immunotherapy for the treatment of unresectable Oesophageal caNcer: a comparative randomized phase II trial
Presenter: Rosine Guimbaud
Session: Poster Display session 2
Resources:
Abstract
1726 - Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Presenter: Kenro Hirata
Session: Poster Display session 2
Resources:
Abstract
2279 - FRONTiER: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Presenter: Shun Yamamoto
Session: Poster Display session 2
Resources:
Abstract
4912 - A phase Ib/II study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined With mXELOX as First-line Therapy for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Jiafu Ji
Session: Poster Display session 2
Resources:
Abstract
3780 - Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Presenter: Salah-Eddin Al-Batran
Session: Poster Display session 2
Resources:
Abstract