Cancers (Jun 2021)
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
- Alessandra Raimondi,
- Federica Palermo,
- Michele Prisciandaro,
- Massimo Aglietta,
- Lorenzo Antonuzzo,
- Giuseppe Aprile,
- Rossana Berardi,
- Giovanni G. Cardellino,
- Giovanni De Manzoni,
- Ferdinando De Vita,
- Massimo Di Maio,
- Lorenzo Fornaro,
- Giovanni L. 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
Affiliations
- Alessandra Raimondi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
- Federica Palermo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
- Michele Prisciandaro
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
- Massimo Aglietta
- Medical Oncology Unit, Candiolo Cancer Institute—FPO, IRCCS, 10060 Candiolo, Italy
- Lorenzo Antonuzzo
- Clinical Oncology Unit, Careggi University Hospital, 50139 Florence, Italy
- Giuseppe Aprile
- Department of Clinical Oncology, Azienda ULSS 8 Berica-Ospedale di Vicenza, 36100 Vinceza, Italy
- Rossana Berardi
- Department of Clinical Oncology, Università Politecnica delle Marche—AOU Ospedali Riuniti di Ancona, 60126 Ancona, Italy
- Giovanni G. Cardellino
- Department of Oncology, Presidio Ospedaliero “Santa Maria della Misericordia”—ASUFC, 33100 Udine, Italy
- Giovanni De Manzoni
- Department of Surgery, Azienda Ospedaliero Universitaria Integrata di Verona—Borgo Trento, 37126 Verona, Italy
- Ferdinando De Vita
- Medical Oncology Unit, Azienda Ospedaliero Universitaria dell’Università degli Studi della Campania “Luigi Vanvitelli”, 80131 Naples, Italy
- Massimo Di Maio
- Department of Oncology, Ospedale Mauriziano Umberto I, 10128 Turin, Italy
- Lorenzo Fornaro
- Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy
- Giovanni L. Frassineti
- Department of Medical Oncology, Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”(IRST)-IRCCS, 47014 Meldola, Italy
- Cristina Granetto
- Medical Oncology, Azienda Ospedaliera S. Croce e Carle, 12100 Cuneo, Italy
- Francesco Iachetta
- Department of Medical Oncology, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
- Sara Lonardi
- Department of Clinical and Experimental Oncology, IRCCS Istituto Oncologico Veneto, 35128 Padua, Italy
- Roberto Murialdo
- Medical Oncology, Ospedale Policlinico San Martino, 16132 Genoa, Italy
- Elena Ongaro
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
- Francesca Pucci
- Medical Oncology Unit, Azienda Ospedaliero Universitaria di Parma, 43126 Parma, Italy
- Margherita Ratti
- Oncology Department, Azienda Socio-Sanitaria Territoriale di Cremona, 26100 Cremona, Italy
- Nicola Silvestris
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 15731 Tabriz, Iran
- Valeria Smiroldo
- Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy
- Andrea Spallanzani
- Medical Oncology Unit, Azienda Ospedaliero Universitaria di Modena, 41125 Modena, Italy
- Antonia Strippoli
- Medical Oncology Unit, Policlinico Universitario A. Gemelli, 00168 Rome, Italy
- Stefano Tamberi
- Medical Oncology, Azienda USL Della Romagna, 48018 Faenza, Italy
- Emiliano Tamburini
- Medical Oncology Unit, Azienda Ospedaliera Cardinale G. Panico, 73039 Tricase, Italy
- Alberto Zaniboni
- Department of Medical Oncology, Fondazione Poliambulanza, 25124 Brescia, Italy
- Maria Di Bartolomeo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
- Chiara Cremolini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
- Carlo Sposito
- Gastrointestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Filippo Pietrantonio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
- DOI
- https://doi.org/10.3390/cancers13112839
- Journal volume & issue
-
Vol. 13,
no. 11
p. 2839
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.
Keywords
- gastric cancer
- microsatellite instability
- pre-operative treatment
- PD-L1
- CTLA4
- non-operative management