Efficacy and safety of QL1706, a novel dual immune checkpoint blockade containing a mixture of anti-PD1 IgG4 and anti-CTLA4 IgG1 antibodies, for advanced nasopharyngeal carcinoma (NPC): Pooled cohort data from phase 1a/1b trials.
Authors: Hongyun Zhao, Yan Huang, Wenfeng Fang, Yuxiang Ma, Yang Zhang, Xiao-Li Wei, Yanhua Yang, Wei Yang, Furong Liu, Zuan Lin, Jianing Li, Li Zhang
Journal: Journal of Clinical Oncology (2022)

6034 Background: Additional anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody could increase the anti-tumor effect of anti-programmed cell death 1 (PD-1) antibody. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies produced by a single cell line. Here the pooled data from phase 1a/1b trials of QL1706 in advanced NPC were reported. Methods: In the phase 1a dose escalation and expansion study (NCT04296994), patients received intravenous QL1706 at 0.3, 1.0, 3.0, 5.0, 7.5, or 10.0 mg/kg q3w for dose escalation in an accelerated 3+3 design, and the dose expansion cohorts received selected doses. In phase 1b (NCT05171790), patients with advanced solid tumors were given intravenous QL1706 5.0 mg/kg q3w according to the data in phase 1a. Phase 1a was primarily aimed to define the safety, tolerability, and recommended phase 2 dose of QL1706, and phase 1b was to evaluate the preliminary efficacy. Pooled analyses were conducted in the NPC cohorts receiving QL1706 5 mg/kg. Additionally, dynamic changes of plasma EBV DNA level from baseline were determined in a part of patients during the studies. Results: As of Dec 31, 2021, totally 110 patients with NPC were included. Median follow-up was 7.7 months. 79 (71.8%) patients had ≥two prior treatment lines. 48 (43.6%) patients received previous immunotherapy. Confirmed overall response was reached in 27 patients (24.5%; 95% CI 16.8%-33.7%). In immunotherapy-naive patients with one and ≥two prior lines of treatment, overall response rates were 39.1% (9/23) and 38.5% (15/39), respectively. Three of 48 (6.3%) immunotherapy-treated patients had partial response. Disease control was observed in 54 (49.1%; 95% CI 39.4%-58.8%) patients. Median duration of response reached 11.7 months (95% CI 8.1-not estimable). Median progression-free survival was 2.0 months (95% CI 1.4-2.9). Overall survival data were immature. Patients with ≥50% decrease in EBV DNA level on day 43 had significantly better ORR than those with &lt; 50% decrease (67% [8/12] versus 12% [2/17]; P = 0.0045). Treatment-related adverse events (TRAE) were reported in 85 (77.3%) patients. 14 (12.7%) experienced grade ≥3 TRAE. The most common TRAE were rash, hypothyroidism (25 [22.7%], each), and pruritus (22 [20%]). TRAE leading to dose interruptions occurred in 10 (9.1%) patients. No TRAE leading to dose discontinuation or death was reported. The immune-related TRAE and serious TRAE were observed in 51 (46.4%) and eight patients (7.3%), respectively. Conclusions: These preliminary results indicated QL1706 had impressive anti-tumor effects on advanced NPC, with acceptable tolerability and manageable toxicity. Further investigation of QL1706 in NPC is continuing. Clinical trial information: NCT04296994; NCT05171790.