Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

Autor: Ning T; Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China., Li D; Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China., Deng T; Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China., Bai Y; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China., Chen Y; Department of Oncology Surgery, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China., Wang Z; Department of Immuno-Oncology, Affiliated Hospital of Hebei University, Shijiazhuang, China., Hu B; Department of biostatistics and SAS programming, Chai Tai Tianqing Pharmaceutical Group Co, Ltd, Nanjing, China., Ba Y; Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Department of Cancer Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China., Lu W; Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2024 Sep 15; Vol. 130 (18), pp. 3137-3146. Date of Electronic Publication: 2024 May 23.
DOI: 10.1002/cncr.35377
Abstrakt: Background: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity.
Methods: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response.
Results: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC.
Conclusions: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.
(© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
Databáze: MEDLINE
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