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.

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 / A. Raimondi, F. Palermo, M. Prisciandaro, M. Aglietta, L. Antonuzzo, G. Aprile, R. Berardi, G.G. Cardellino, G. De Manzoni, F. De Vita, M. Di Maio, L. Fornaro, G.L. Frassineti, C. Granetto, F. Iachetta, S. Lonardi, R. Murialdo, E. Ongaro, F. Pucci, M. Ratti, N. Silvestris, V. Smiroldo, A. Spallanzani, A. Strippoli, S. Tamberi, E. Tamburini, A. Zaniboni, M. Di Bartolomeo, C. Cremolini, C. Sposito, V. Mazzaferro, F. Pietrantonio. - In: CANCERS. - ISSN 2072-6694. - 13:11(2021 Jun 07), pp. 2839.1-2839.15. [10.3390/cancers13112839]

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

M. Prisciandaro;C. Sposito;V. Mazzaferro;F. Pietrantonio
2021

Abstract

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.
CTLA4; Gastric cancer; Microsatellite instability; Non-operative management; PD-L1; Pre-operative treatment
Settore MED/18 - Chirurgia Generale
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/872329
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