373O - First-line iparomlimab and tuvonralimab (QL1706) + chemotherapy (chemo) ± bevacizumab (BEV) for recurrent or metastatic cervical cancer (r/mCC): Updated results of the phase II DUBHE-C-204 study

Background

QL1706 is a bifunctional MabPair product of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies. The DUBHE-C-206 study has confirmed effectiveness of second- or higher-line QL1706 for r/mCC. The DUBHE-C-204 study (NCT05179317) evaluated safety and efficacy of first-line QL1706 + chemo ± BEV for r/mCC. The primary results have been published. Here, we report the updated results.

Methods

In this single-arm phase II study, r/mCC patients (pts) who had not received prior systemic treatment were enrolled. Pts received intravenous QL1706 (5 mg/kg, D1), paclitaxel (175 or 135 mg/m², D1), cisplatin (50 mg/m², D1 or D2)/carboplatin (area under the concentration-time curve = 5, D1) without (Cohort 1) or with BEV (15 mg/kg, D1 or D2; Cohort 2) of a 21-day cycle for six cycles. Then, QL1706 ± BEV was given as maintenance treatment. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) via RECIST v1.1, and overall survival (OS).

Results

From Jun 2021 to Mar 2022, 60 pts were enrolled for safety analysis (30 in each cohort). 58 pts were analyzed for efficacy (28 in Cohort 1; 30 in Cohort 2). As of Jun 25, 2024, median follow-up was 27.0 months. Grade ≥3 treatment-related adverse events (TRAE) occurred in 45 pts (75.0%), with the most common being neutrophil count decreased (23 [38.3%]), white blood cell count decreased (20 [33.3%]), and lymphocyte count decreased (11 [18.3%]). Serious TRAE, TRAE leading to discontinuation, and grade ≥3 immune-related adverse events occurred in 22 (36.7%), 19 (31.7%), and 9 (15.0%) pts, respectively. Consistent with previous report, ORR was 81.0% (47 pts), and DCR was 98.3% (57 pts). Median PFS and OS were 15.1 months (95% CI 9.2–20.2) and not reached (21.9–not evaluable), respectively. In Cohort 1 and 2, median PFS were 14.3 and 16.4 months, and median OS were both not reached, respectively.

Conclusions

First-line QL1706 + chemo ± BEV for r/mCC were safe and effective. The BEV-including regimen may bring longer PFS. A phase III study of first-line QL1706 + chemo ± BEV r/mCC is ongoing.

Clinical trial identification

NCT05179317; Jan 05, 2022.

Editorial acknowledgement

We thank Yunjie Yu (Qilu Pharmaceutical Co., Ltd.) for providing medical writing support.

Legal entity responsible for the study

Qilu Pharmaceutical Co., Ltd. (Jinan, China).

Funding

Qilu Pharmaceutical Co., Ltd. (Jinan, China).

Disclosure

X. Zhang, S. Xue, X. Kang: Financial Interests, Personal, Full or part-time Employment: Qilu Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.