Anlotinib combined with TQB2450 in patients with platinum-resistant or -refractory ovarian cancer: A multi-center, single-arm, phase 1b trial

Chun-Yan Lan, Jing Zhao, Fan Yang, Ying Xiong, Rong Li, Yu Huang, Jing Wang, Chang Liu, Xue-Han Bi, Hai-Hong Jin, Jin Meng, Wei-Hong Zhao, Li Zhang, Ya-Fei Wang, Min Zheng, Xin Huang, Chun-Yan Lan, Jing Zhao, Fan Yang, Ying Xiong, Rong Li, Yu Huang, Jing Wang, Chang Liu, Xue-Han Bi, Hai-Hong Jin, Jin Meng, Wei-Hong Zhao, Li Zhang, Ya-Fei Wang, Min Zheng, Xin Huang

Abstract

This is a phase Ib study of anlotinib plus a programmed death-ligand 1 (PD-L1) inhibitor TQB2450 for platinum-resistant or -refractory ovarian cancer. Thirty-four patients are enrolled and receive treatment. The objective response rate (ORR) is 47.1%, and the disease control rate is 97.1%. The median duration of response (DOR) has not been reached, and 61.3% of patients have a DOR of at least 8 months. The median progression-free survival (PFS) is 7.8 months, and the median overall survival (OS) has not been reached. The PD-L1-positive group has an ORR of 25.0%, whereas the PD-L1-negative group has an ORR of 92.9%. Treatment-related grade 3 or 4 adverse events (AEs) occur in 70.6% of patients, with the most common being hypertension (29.4%) and palmar-plantar erythrodysesthesia syndrome (29.4%). Anlotinib plus TQB2450 show promising antitumor activity and manageable toxicities in patients with platinum-resistant or -refractory ovarian cancer. A phase 3 randomized controlled trial to further validate our findings is ongoing.

Trial registration: ClinicalTrials.gov NCT04236362.

Keywords: PD-1 inhibitor; PD-L1 inhibitor; TQB2450; VEGFR inhibitor; anlotinib; immune checkpoint inhibitor; immunotherapy; ovarian cancer; platinum-resistant; targeted therapy.

Conflict of interest statement

Declaration of interests Y.-F.W. is an employee of Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Trial profile
Figure 2
Figure 2
Tumor response assessment with waterfall plot and treatment duration with swimmer plot (A) Waterfall plot for best percentage change in target lesion size. The patients who had at least one post-baseline tumor assessment were included (n = 33). The dashed line at −30% change represents the RECIST 1.1 cutoff to define partial response or complete response. (B) Swimmer plot. The length of each bar represents the duration treatment for each patient.
Figure 3
Figure 3
Kaplan-Meier curves of duration of response, progression-free survival, and overall survival Kaplan-Meier curves of (A) duration of response, (B) progression-free survival, and (C) overall survival. NE, not estimable.
Figure 4
Figure 4
Kaplan-Meier curves of progression-free survival of PD-L1-positive and -negative tumors. NE, not estimable; HR, hazard ratio. See also Table S3.

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