[ASCO Daily News] Novel IO Approaches Demonstrate High pCR Rates in the Neoadjuvant Setting, Questioning the Need for Surgery in Certain Patients With CRC

June 04, 2024

IBI310 Plus Sintilimab Induces Robust Responses in Locally Advanced dMMR Colorectal Cancer

Dr. Xu and collaborators evaluated the neoadjuvant treatment of IBI310, an anti–CTLA-4 antibody, plus sintilimab, an anti–PD-1 antibody, in patients with previously untreated locally advanced stage IIb-III MSI-high/dMMR colorectal cancer (Abstract 3505).

This phase 1b study enrolled 101 patients as of February 4, 2024, and randomly assigned them to either 1 cycle of IBI310 1 mg/kg plus 2 cycles of sintilimab 200 mg once every 3 weeks (arm A) or 2 cycles of sintilimab 200 mg once every 3 weeks as neoadjuvant treatment (arm B). The stratification factors were risk evaluation at baseline and age. Patients had curative resection between days 36 and 56 after the first dose of neoadjuvant treatment. pCR rate served as the primary endpoint.

Patients in arm A had a pCR rate of 80.0%, whereas patients in arm B had a pCR rate of 47.7%. Importantly, “there were no new safety concerns with these drugs,” Dr. Xu said.

Grade 3 or higher treatment-emergent adverse events occurred in 26.9% of patients in arm A receiving combination treatment and 18.4% of patients in arm B receiving sintilimab only. All patients were able to go on to surgery.

Although the duration of follow-up was not long enough to evaluate the overall survival and disease-free survival in these 2 patient groups, Dr. Xu is optimistic that the higher pCR rates seen with the combination of IBI310 and sintilimab could translate into longer survival for patients treated with this combination. Dr. Xu’s group has recently opened a phase 3 trial that will include a longer follow-up as well as survival endpoints. According to Dr. Xu, if the findings from this trial turn out to be positive, they may lead to a shift in the standard of care for this group of patients with colorectal cancer from the current chemotherapy and surgery to IBI310 plus sintilimab, followed by surgery.

“Maybe most of the patients can be cured with just neoadjuvant therapy without a need for surgery,” he said. “I think this could be possible, but we still need to accumulate more data.”

Dr. Ciombor, who served as the discussant for Abstract 3505, noted that the strength of this study lies in the head-to-head comparison of doublet therapy versus monotherapy and the fact that it showed “a significant improvement in [pCR] rates in the patients who got the combination versus sintilimab alone….and that was both in the intent-to-treat as well as the ‘per protocol’ groupings of patients.”

She added that, based on these findings and a manageable safety profile of the combination, it is reasonable to move from phase 1b to phase 3.

Dr. Sen noted that this study demonstrates that patients who received a “dual checkpoint inhibitor strategy―a CTLA-4 inhibitor plus PD-L1 inhibitor―had a much higher [pCR] rate compared to patients who got the PD-L1 inhibitor by itself. [The authors] demonstrate that there generally weren’t delays in getting to surgery or side effects that appeared to either delay surgery or lead to worse outcomes in these patients….with a big exception of 1 patient in the combination arm who died of myocarditis.”

— Jasenka Piljac Žegarac, PhD

Source: ASCO Daily News     

Link to the original report at ASCO Daily News

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