Anti-PD-L1 envafolimab combined with anti-VEGF suvemcitug in pretreated solid tumors and hepatocellular carcinoma: an open-label phase II study with safety run-in stage
- Invest New Drugs. 2025 Apr;43(2):181-190. doi: 10.1007/s10637-025-01506-x.
- 1. Department of Internal Medicine, Jilin Cancer Hospital, Changchun, China.
- 2. Department of Oncology, Mianyang Central Hospital, Mianyang, China.
- 3. Medical Oncology Dept, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- 4. Department of Hepato-Pancreato-Biliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, MinistryofEducation/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
- 5. Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- 6. Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
- 7. Department of Medical Oncology, Zhejiang Provincial People's Hospital, Hangzhou, China.
- 8. Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
- 9. Clinical Science, Shandong Simcere Biopharmaceutical Co., Ltd, Shandong, China.
- 10. State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China.
- 11. Clinical Pharmacology, Shandong Simcere Biopharmaceutical Co., Ltd, Shandong, China.
- 12. Clinical Statistics, Shandong Simcere Biopharmaceutical Co., Ltd, Shandong, China.
- 13. Department of Internal Medicine, Jilin Cancer Hospital, Changchun, China. [email protected].
- 14. Department of Thoracic Oncology, Jilin Cancer Hospital, No.1066 Jinhu Road, Changchun City, Jilin Province, 130000, China. [email protected].
Background: Immune checkpoint inhibitors (ICIs) combined with anti-vascular endothelial growth factor (VEGF) have been the standard first-line treatment of hepatocellular carcinoma (HCC). However, the efficacy of this combination in post-line treatment is still unknown. This study aimed to evaluate the efficacy and safety of the combination of anti-PD-L1 envafolimab and novel humanized anti-VEGF suvemcitug as second-line treatment for patients with HCC.
Methods: This open-label, prospective phase II clinical study (NCT05148195) comprised safety run-in stage and dose expansion stage of HCC cohort. Eligible patients were aged ≥ 18 years and had undergone at least a prior line of treatment. Patients received fixed-dose envafolimab and suvemcitug until termination of disease progression, unacceptable toxicities, or withdrawal. The primary endpoint of safety run-in stage was recommended dose (RD), and dose expansion stage was objective response rate (ORR).
Results: As of August 10, 2023, no dose-limiting toxicity was observed in six patients in the safety-run-in stage, and 2 mg/kg dose every 3 weeks was declared the RD of suvemcitug. Among 20 patients with HCC, the median age was 54.5 (range, 42-70) years. Of these patients, 20 (100.0%) received ≥ one prior line treatment, with 20 (100%) received tyrosine kinase inhibitor (TKI) treatment and 8 (40.0%) received prior ICI treatment. The ORR was 10.0% (95% confidence interval (CI), 1.2-31.7), DCR was 65.0% (95% CI, 40.8-84.6), and DoR was not reached (NR). With a median follow-up of 13.9 months, the median progression-free survival (PFS) and median overall survival (OS) were 4.3 months (95% CI, 1.4-8.1) and 10.7 months (95% CI, 6.0-not evaluable [NE]), respectively. Treatment-related adverse events (TRAEs) of grade ≥ 3 occurred in 40% patients, with proteinuria (20.0%, 4/20) being the most frequent. The ORR of no lung metastasis, prior first-line treatment and IO naïve treatment subgroup was 16.7%.
Conclusions: The combination of envafolimab and suvemcitug showed a tolerable safety profile and promising antitumor activity in HCC patients who failed later-line treatment.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: VEGFR