Abstract 77P
Background
Patients (pts) with microsatellite stable (MSS)/microsatellite instability (MSI)-low mCRC treated by first-line chemotherapy (chemo) have poor outcomes. This study explored QL1706, a dual blocker targeting both programmed cell death-1 and cytotoxic T lymphocyte-associated antigen-4 pathways, in the first-line treatment of mCRC.
Methods
This multicenter single-arm phase II trial recruited previously untreated pts with unresectable locally advanced or mCRC. MSI-high pts regardless of RAS/BRAF status were included in Cohort 1 (C1) and administered 5 mg/kg QL1706 intravenously every three weeks (Q3W). MSS/MSI-low and wild-type RAS/BRAF pts were included in Cohort 2 (C2) and administered 5 mg/kg QL1706, 7.5mg/kg bevacizumab, oxaliplatin, and capecitabine Q3W. The primary endpoint was objective response rate (ORR) per investigator according to Response Evaluation Criteria in Solid Tumors v1.1.
Results
From Aug 5, 2022 to Jul 14, 2023, eight and 51 pts were included in full analysis set of C1 and C2, respectively. Eastern Cooperative Oncology Group performance status was 1 in six (75%) pts in C1 and 43 (84%) in C2. As of Apr 15, 2024, the median follow-up time was 10.7 (range, 1.6-16.6) months. In C1, five partial response (PR) pts maintained response over 12 months. ORR was 62.5%, and disease control rate (DCR) was 100%. In C2, 36 pts had PR. ORR was 70.6% (95% confidence interval [CI] 56.2%-82.5%), and DCR was 96.1% (95% CI 86.5%-99.5%). The median duration of response was not reached. Two PR pts were indicated for surgery of radical resection. In C1, two pts had ≥grade 3 treatment-related adverse events (TRAEs), one hypertriglyceridemia and one QL1706-related ketoacidosis causing treatment discontinuation. In C2, 35 (68.6%) pts had ≥grade 3 TRAEs (54.9% chemo-related). Eighteen (35.3%) pts discontinued treatment due to TRAEs (17.6% chemo-related). The most common TRAE and ≥grade 3 TRAE was neutrophil count decreased (any grade: 58.8%; ≥grade 3: 23.5%).
Conclusions
QL1706 showed sustainable response in pts with MSI-high mCRC. QL1706-combined therapy showed high ORR and tolerability in pts with MSS/MSI-low mCRC. No new safety signal was observed with QL1706 or its combined therapy.
Clinical trial identification
NCT05799820.
Editorial acknowledgement
Legal entity responsible for the study
Qilu Pharmaceutical Co., Ltd.
Funding
Qilu Pharmaceutical Co., Ltd.
Disclosure
Z. Wang, M. Si, L. Li, X. Kang: Other, Personal, Full or part-time Employment: Qilu Pharmaceutical. All other authors have declared no conflicts of interest.