Efficacy and safety of HLX10, a novel anti-PD-1 antibody, in patients with previously treated unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumors: A single-arm, multicenter, phase 2 study.

2566 Background: Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) in cells render them susceptible to immune checkpoint blockages. This study aimed to evaluate the efficacy and safety of HLX10, a fully humanized monoclonal antibody against PD-1, in patients with unresectable or metastatic MSI-H/dMMR solid tumors who have progressed on or been intolerant to standard therapies. Methods: In this single-arm, open-label, multicenter, phase 2 study (NCT03941574), patients (18≤ age ≤75 years) with histologically/cytologically confirmed unresectable or metastatic MSI-H/dMMR solid tumors were recruited to receive 3 mg/kg HLX10 every two weeks intravenously for up to 2 years until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by IRRC (evaluated every 6 weeks for the first 48 weeks and every 12 weeks thereafter) per RECIST v1.1. Secondary endpoints included ORR assessed by investigators, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. All eligible patients who received at least one dose of HLX10 were included in the safety analyses. Results: As of Jan 9, 2021, 108 patients were enrolled and 68 with locally or centrally confirmed MSI-H were included in the main efficacy analysis population. Among the 68 patients, the median follow-up duration was 7.7 (range: 1.1–16.4) months and the median age was 53.0 (range: 23.0–72.0) years. MSI-H tumor types included colorectal cancer (n = 54), endometrial cancer (n = 5), gastric cancer (n = 4), breast cancer (n = 2), small intestine cancer (n = 2) and fallopian tube cancer (n = 1). IRRC and investigator assessed ORR were 38.2% (95% CI: 26.7–50.8%; 2 complete response) and 35.3% (95% CI: 24.1–47.8%) respectively in the main efficacy analysis population. Median DoR, PFS and OS have not been reached. 105 (97.2%) patients experienced treatment-emergent adverse events (TEAEs), most commonly anemia (34.3%), hypoproteinemia (27.8%) and increased aspartate aminotransferase (25.0%). 53 (49.1%) patients had grade 3 or worse TEAEs, most commonly anemia (8.3%), progressive disease (6.5%), increased γ- glutamyltransferase (5.6%) and intestinal obstruction (5.6%). 52 (48.1%) patients had immune-related adverse events (irAEs) while 10 (9.3%) had grade 3 or worse irAEs. 3 (2.8%) deaths (2 PD and 1 intestinal obstruction) that might be related to the study drug were reported. Conclusions: HLX10 provides encouraging antitumor activity with a manageable safety profile in patients with MSI-H/dMMR solid tumors who have progressed on or been intolerant to standard therapies. As an effective tissue-agnostic treatment, HLX10 possesses the potential to improve patients’ clinical outcomes. Clinical trial information: NCT03941574.