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TremelImumab and Durvalumab Combination for the Non-OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-Arm, Multi-Cohort, Phase II INFINITY Study

2021; Multidisciplinary Digital Publishing Institute; Volume: 13; Issue: 11 Linguagem: Inglês

10.3390/cancers13112839

2072-6694

Alessandra Raimondi, Federica Palermo, Michele Prisciandaro, Massimo Aglietta, Lorenzo Antonuzzo, Giuseppe Aprile, Rossana Berardi, Giovanni Gerardo Cardellino, Giovanni De Manzoni, Ferdinando De Vita, Massimo Di Maïo, Lorenzo Fornaro, Giovanni Luca Frassineti, Cristina Granetto, Francesco Iachetta, Sara Lonardi, Roberto Murialdo, Elena Ongaro, Francesca Pucci, Margherita Ratti, Nicola Silvestris, Valeria Smiroldo, Andrea Spallanzani, Antonia Strippoli, Stefano Tamberi, Emiliano Tamburini, Alberto Zaniboni, Maria Di Bartolomeo, Chiara Cremolini, Carlo Sposito, Vincenzo Mazzaferro, Filippo Pietrantonio,

Colorectal and Anal Carcinomas

In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.