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 cervical cancer: Cohort data from a phase 1b trial.

5535 Background: Anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and anti-programmed cell death 1 (PD-1) antibodies have synergistic effect. 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. QL1706 showed promising anti-tumor activity in multiple solid tumors. Here we reported the cervical cancer cohort data from the phase 1b trial of QL1706 (NCT05171790). Methods: Eligible patients had a pathologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, with recurrent or metastatic, immunotherapy-naive disease at the time of enrollment. Patients were required to have ≥one lesion measurable by RECIST v1.1 and disease that had relapsed after a first-line, platinum-based regimen. Patients were included regardless of PD-L1 expression status at baseline. Patients received intravenous QL1706 5.0 mg/kg q3w (i.e., recommended phase 2 dose, defined in a phase 1a trial), for up to 24 months. The primary endpoint was confirmed overall response rate (ORR) per RECIST v1.1 by investigator. The secondary endpoints included disease control rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, etc. Results: As of Dec 31, 2021, totally 53 patients with cervical cancer were enrolled (median age, 52 years [range 33-72]). Median follow-up was 5.6 months. Most patients (45 [85%]) had ECOG performance status of 1. Histological breakdown was squamous cell carcinoma (44 [83%]) and adenocarcinoma (nine [17%]). 33 (62%) patients had received one prior chemotherapy, 20(38%) patients had received ≥two prior chemotherapy. The confirmed ORR was 28% (95% CI 17%-42%; 15 patients), including one (2%) complete response and 14 (26%) partial response, with median duration of response not reached (95% CI 2.8 months-not estimable). Disease control was observed in 29 (55%; 95% CI 40%-68%) patients. Median PFS was 4.2 months (95% CI 1.7-6.9), and 6-month PFS rate was estimated as 37% (95% CI 24%-51%). Treatment-related adverse events (TRAE) were observed in 40 (75%) patients. Nine (17%) experienced grade ≥3 TRAE. The most common TRAE were rash (eight [15%]), hyperthyroidism (eight [15%]), and pyrexia (seven [13%]). Three (6%) patients suffered TRAE leading to dose discontinuation. The immune-related TRAE and serious TRAE were observed in 28 (53%) and eight (15%) patients, respectively. Conclusions: QL1706 demonstrated promising and durable clinical activity, with favorable tolerability in patients with recurrent and/or metastatic cervical cancer. Further investigations in this setting are continuing. Clinical trial information: NCT05171790.