Neoadjuvant treatment of QL1706 in patients with resectable microsatellite instability-high/mismatch repair-deficient colon cancer: Results from a phase 1b trial.
Year: 2026
Type: conference-abstract
Abstract: 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 .
Source: Journal of Clinical Oncology
Institutions: Sun Yat-sen University, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Shandong Provincial Hospital, Shandong First Medical University, Qilu Pharmaceutical Co., Ltd. (China), Henan Cancer Hospital, Guangxi Medical University, Tumor Hospital of Guangxi Medical University, Third Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Nanchang University, Sichuan University, West China Hospital of Sichuan University, Jiangmen Central Hospital, Shanxi Medical University, Chinese Academy of Medical Sciences & Peking Union Medical College, Shanxi Provincial Cancer Hospital, Zhejiang Cancer Hospital, Hunan Cancer Hospital, Shandong Tumor Hospital, Ganzhou People's Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7162535950
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