251 Efficacy and safety of iparomlimab and tuvonralimab in previously treated patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase 2 clinical trial (DUBHE-C-206)

Introduction/Background

Iparomlimab and tuvonralimab (QL1706), a bifunctional PD-1/CTLA-4 dual blocker, showed preliminary efficacy in patients with cervical cancer in phase 1 trial.

Methodology

This multi-center, open-label, single-arm, phase 2 trial (NCT05557565) recruited immune checkpoint inhibitors naïve patients with recurrent or metastatic cervical cancer (r/m CC) who failed first-line platinum-based chemotherapy with or without bevacizumab, regardless of PD-L1 status. Intravenous injection of iparomlimab and tuvonralimab 5.0 mg/kg every three weeks was administered. The primary endpoint was objective response rate (ORR) evaluated by the independent review committee (IRC).

Results

As of April 28, 2023, 148 participants were included in the full analysis set. Eastern Cooperative Oncology Group Performance Status scored 1 in 109 (73.6%) patients. Fifty-nine (39.9%) patients received prior bevacizumab. Fifty-five patients (37.2%) had received ≥2 lines of prior treatment. Median follow-up was 11.0 (0.7, 15.5) months. Per IRC, ORR was 33.8% (95% confidence interval [CI]: 26.2%-42.0%), and disease control rate was 64.9% (95% CI: 56.6%-72.5%). Median progression-free survival achieved 5.4 month (95% CI: 3.9–6.9). Median overall survival was not reached. ORR was 25.6% (95% CI: 13.5–41.2) and 37.1% (95% CI: 27.9%-47.1%) in patients with combined positive score (CPS) <1 (n=43) and with CPS≥1 (n=105), respectively. Treatment-related adverse events (TRAE) occurred in 104 (70.3%) patients. TRAE of grade ≥3 occurred in 36 (24.3%) patients, and the most common were anemia (4.1%), gamma-glutamyl transferase increased (2.7%), and lipase increased (2.7%). Three (2.0%) participants had TRAE leading to treatment discontinuation. Nine (6.1%) participants died due to treatment-emergent adverse events, which were all unrelated to the treatment.

Conclusion

Iparomlimab and tuvonralimab showed promising efficacy and manageable safety in patients with r/m CC who failed first-line chemotherapy. A phase 3 trial (NCT05446883) evaluating iparomlimab and tuvonralimab plus chemotherapy as first-line treatment for r/m CC is ongoing.

Disclosures

The presenting author, Jihong Liu, and the co-authors Hanmei Lou, Yun Zhou, Dapeng Li, Hongping Zhang, Mingjun Zhang, Lihua Wang, Huijun Cheng, Zi Liu, Wei Duan, and Mei Feng, declare that they have no conflict of interest. The co-authors Chao Wang, Shilin Xue, Hui Li, and Xiaoyan Kang are full-time employees of the company Qilu Pharmaceutical Co., Ltd.