Neoadjuvant treatment of QL1706 in patients with resectable microsatellite instability-high/mismatch repair-deficient colon cancer: Results from a phase 1b trial.

3620 Background: Immune checkpoint inhibitors in neoadjuvant setting have brought clinical benefits for patients with various tumors. This study aimed to evaluate the efficacy and safety of iparomlimab and tuvonralimab (QL1706), a bifunctional antibody targeting both PD-1 and CTLA-4, as neoadjuvant treatment in patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) colon cancer. Methods: In this single-arm phase 1b trial, previously untreated patients with resectable stage IIb-III MSI-H/dMMR colon cancer were recruited. Patients were administered neoadjuvant treatment of QL1706 at 5 mg/kg via intravenous infusion every three weeks for four cycles. Radical resection was scheduled between 4 and 6 weeks after last dose of neoadjuvant treatment. The primary endpoint was pathological complete response (pCR) rate. The efficacy analysis set included patients who were confirmed dMMR/MSI-H, received at least one dose of treatment, and had post-surgery pathological results. The safety analysis set included patients who received at least one dose of treatment. Results: As of data cut-off date on Oct 15, 2025, 43 patients were enrolled (median age: 56.0 years; males: 58.1%; ECOG PS 1: 55.8%; Lynch syndrome: 34.9%). Scheduled radical resection were performed in 34 patients. A total of 34 patients were included in the efficacy analysis set. The pCR rate was 88.2% (30/34, 95% confidence interval [CI]: 72.5%-96.7%). The major pathologic response rate was 91.2% (31/34, 95% CI: 76.3%-98.1%). In high-risk patients (T4 or N2), the pCR rate was 86.4% (19/22, 95% CI: 65.1%-97.1%). All patients (100%) received surgery had R0 resection. Median treatment exposure was 2.1 months (range, 0.0-3.9). Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 12 patients (27.9%); two (4.7%) patients were treatment-related. Immune-related adverse events grade ≥3 occurred in two (4.7%) patients, including one grade 3 acute kidney injury and one grade 4 hypersensitivity, both of which recovered finally. Treatment-related serious adverse events occurred in three (7.0%) patients. No patient cancelled or delayed the surgery due to TEAE. No TEAE leading to death occurred. The incidence of grade ≥3 TEAE during the surgery phase was 11.8% (4/34). Conclusions: Neoadjuvant treatment of QL1706 showed promising pCR rate and manageable safety in patients with MSI-H/dMMR colon cancer. A phase 3 trial is ongoing to further confirm the efficacy and safety of QL1706 as neoadjuvant treatment in patients with resectable MSI-H/dMMR colon cancer. Clinical trial information: NCT06686576 .