Tremelimumab and Durvalumab as Neoadjuvant or Non-Operative Management Strategy of Patients With Microsatellite Instability-High Resectable Gastric or Gastroesophageal Junction Adenocarcinoma: The INFINITY Study by GONO

12/03/2024

Tremelimumab and Durvalumab as Neoadjuvant or Non-Operative Management Strategy of Patients With Microsatellite Instability-High Resectable Gastric or Gastroesophageal Junction Adenocarcinoma: The INFINITY Study by GONO

Annals of Oncology

Authors A. Raimondi, S. Lonardi, S. Murgioni, G.G. Cardellino, S. Tamberi, A. Strippoli, F. Palermo, G. De Manzoni, M. Bencivenga, A. Bittoni, C. Chiodoni, D. Lorenzini, K. Todoerti, P. Manca, S. Sangaletti, M. Prisciandaro, G. Randon, F. Nichetti, F. Bergamo, S. Brich, A. Belfiore, A. Bertolotti, D. Stetco, A. Guidi, T. Torelli, A. Vingiani, R.P. Joshi, M. Khoshdeli, N. Beaubier, M.C. Stumpe, F. Nappo, A.G. Leone, C.C. Pircher, G. Leoncini, G. Sabella, L. Airo’ Farulla, A. Alessi, F. Morano, A. Martinetti, M. Niger, M. Fassan, M. Di Maio, K. Kaneva, M. Milione, H. Nimeiri, C. Sposito, L. Agnelli, V. Mazzaferro, M. Di Bartolomeo, and F. Pietrantonio

Background

In resectable gastric/gastroesophageal junction adenocarcinoma (GAC/GEJAC), microsatellite instability (MSI-H) confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need of chemotherapy or surgery.

Patients and methods

INFINITY is a multicentre, multicohort phase II trial (NCT04817826) investigating in Cohort 1 the activity and safety of tremelimumab+durvalumab (T300/D) as neoadjuvant treatment for dMMR/MSI-H, resectable GAC/GEJAC. Primary endpoint was pathologic complete response (pCR) rate; Secondary endpoints: progression-free survival (PFS), overall survival (OS), quality of life (QoL), and translational analyses. In Cohort 2, the activity and safety of T300/D was explored as definitive treatment in patients achieving clinical complete response (cCR). Primary endpoint was 2-year cCR rate, Secondary endpoints: PFS, OS, QoL, gastrectomy-free survival (GFS) and translational analyses.

Results

In Cohort 1, 18 patients were recruited and 15 evaluable. pCR and major-complete pathological response were 60% and 80%. Since pCR rate in T4 tumors was 17%, this subgroup of patients was excluded from enrollment in Cohort 2. At 28.1 months median follow-up, 24-month GC-specific PFS and OS rates were 85% and 92%. In Cohort 2, 18 patients were enrolled and 17 evaluable, 13 had cCR and started non-operative management (NOM). At 11.5 months median follow up, 1 patient had local regrowth and underwent salvage surgery, 12-month GFS was 64.2%.

Conclusions

The INFINITY study provided promising activity results of a chemo-free T300/D combination regimen as pre-operative treatment in dMMR/MSI GAC/GEJAC and the first available feasibility results of a NOM strategy in this disease setting, worth of further validation in larger cohorts.

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