BackgroundEffective 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.MethodsIn 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.ResultsBetween 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.ConclusionsCombined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC. This single-arm, multicenter, open-label, phase 1b cohort trial aimed to estimate the safety and efficacy of anti-PD-L1 antibody TQB2450 and tyrosine kinase receptor inhibitor AL2846 combination therapy in patients with immunotherapy-refractory advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC). The combination therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.
[1]Tianjin Med Univ Canc Inst & Hosp, Tianjins Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy,Dept Gastrointestin, Tianjin Key Lab Digest Canc,Natl Clin Res Ctr Canc, Tianjin 300060, Peoples R China.
[2]Harbin Med Univ, Canc Hosp, Dept Med Oncol, Harbin, Peoples R China.
[3]Henan Univ Sci & Technol, Coll Clin Med, Affiliated Hosp 1,Med Coll, Henan Key Lab Canc Epigenet,Canc Hosp,Dept Oncol S, Luoyang, Peoples R China.
[4]Hebei Univ, Affiliated Hosp, Dept Immuno Oncol, Shijiazhuang, Peoples R China.
[5]Chai Tai Tianqing Pharmaceut Grp Co Ltd, Dept Biostat & SASprogramming, Nanjing, Peoples R China.
[6]Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Canc Ctr, Beijing 100010, Peoples R China.
[7]Tianjin Med Univ Canc Inst & Hosp, Liver Canc Ctr,Dept Hepatobiliary Oncol, Key Lab Canc Prevent & Therapy, Natl Clin Res Ctr Canc,Tianjins Clin Res Ctr Canc, Tianjin 300060, Peoples R China.
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