ASCO GI 2023 | INFINTY: tremelimumab and durvalumab in MSI-high GC/GEJC

I presented today the results of the cohort one of INFINITY study, which is a trial sponsored by the GONO Foundation in Italy. Some background about the trial microsatellite instability is associated with better survival and potential lack of benefit from chemotherapy in patients with resectable gastric, or GE junction, cancer, and it is one of the strongest predictors of the efficacy of immunotherapy. Also, we know that a single high dose of tremelimumab added to durvalumab is able to induce a higher T cell expansion and is approved for patients with hepatocellular carcinoma. In early stage disease for gastric cancer, the activity of immunotherapy is even higher, as in most GI cancers, so immune checkpoint inhibitors may allow the omission of chemotherapy, radiotherapy, or even surgery. The INFINITY trial was designed to test this regimen of tremelimumab and durvalumab as neoadjuvant or definitive treatment. The trial enrolled patients with MSI-high or deficient mismatch repair resectable gastric cancer. Patients were treated with this regimen and for three months, and after disease rest staging, patients in cohort one received surgery and standard follow up. Whereas now the results have been evaluated by an independent data monitoring committee, and enrollment in cohort two has started to evaluate this regimen as non-operative management strategy. The results of cohort one – the primary endpoint was pathological complete response associated with the negative minimal residual disease before surgery. Among all evaluable patients, we enrolled 18 patients, but the evaluable patients were actually 15, the PCR rate was 60% and the rate of complete major to complete pathological response was 80%. So quite encouraging for a subsequent non-operative management cohort. The treatment was well tolerated, so no major safety issues were reported, and also the quality of life was maintained during treatment. Basically, this trial is important because we have now more data in MSI-high gastric cancer demonstrating the safety of immunotherapy combination and also the promising eradicating activity of these regimens with potential future applications for non-operative management. Of course, we know that larger studies are needed, but soon this regimen will represent a standard of care, even if we still don’t know the optimal combination, treatment duration, and the treatment goal, of course, whether it is neoadjuvant or non-operative management organ preservation strategy. Now the enrollment in cohort two INFINITY trial is ongoing after the eDMC evaluation and the protocol amendment to exclude the T4 tumors because we observe very low PCR rate in the T4 subgroup, so we excluded these patients for the future non-operative management strategy.