Abstract 423P
Background
In resectable GAC/GEJAC, MSI is associated with improved survival and potential lack of benefit from chemotherapy. Given the exceptional immune-sensitivity of MSI tumors, immunotherapy induces deep pathological responses that may allow to omit chemotherapy and/or surgery.
Methods
INFINITY is a multicentre, multicohort phase II trial (NCT04817826) investigating activity and safety of tremelimumab+durvalumab (T300/D) as neoadjuvant or definitive (Cohort 1 and 2) treatment for MSI, EBV-negative resectable GAC/GEJAC. All pts received single-dose tremelimumab 300 mg plus durvalumab 1500 mg q4 weeks for 3 cycles. In Cohort 1 all pts underwent surgery; in Cohort 2, for clinical complete response (cCR), namely no evidence of tumor at radiologic-endoscopic restaging and liquid biopsy for minimal residual disease, pts undergo non-operative management (NOM), for disease persistence/relapse they receive surgery. For Cohort 2 the primary endpoint is 2-year cCR rate, secondary endpoints: safety, disease-free survival (DFS), overall survival (OS), gastrectomy-free survival, quality of life (QoL).
Results
In Cohort 1, among 15 evaluable pts 1 had disease progression and 14 underwent resection. pCR rate was 60% and major-complete pathological response rate was 80%. At extended follow-up of 28 months, 24-month gastric cancer specific-PFS and OS rates were 76% and 80%. In Cohort 2, 18 pts were enrolled, 1 had grade 2 toxicity and decided to undergo surgery. Among 17 evaluable pts, 13 (76%) had cCR and started NOM and 4 (24%) did not have cCR and underwent surgery. At median follow up of 8 months, only 1 patient had an early tumor re-growth during NOM and underwent salvage surgery, with a 12-month gastrectomy-free survival of 78%. Any grade and grade ≥3 immune-related adverse events (AEs) occurred in 13 and 3 pts, all resolved with treatment as per protocol. No significant detriment on QoL was shown.
Conclusions
Pre-operative or definitive T300/D for 3 months was safe in MSI dMMR GAC/GEJAC pts and showed the potential opportunity to omit surgery in selected pts with cCR.
Clinical trial identification
NCT04817826; Released on 23 March 2021.
Legal entity responsible for the study
GONO (Gruppo Oncologico del Nord Ovest) Foundation.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.