catequentinib

Overview

Catequentinib (marketed and widely studied under the name anlotinib; also known as AL3818) is a novel, orally administered small-molecule multi-target tyrosine kinase inhibitor (TKI) with broad antitumor activity. It exerts its pharmacological effects by simultaneously blocking multiple receptor tyrosine kinases involved in tumor angiogenesis, proliferation, and survival, including vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), and c-Kit. By concurrently inhibiting these overlapping signaling axes, catequentinib disrupts tumor neovascularization and directly suppresses tumor cell proliferation, offering a mechanistic rationale for its use across a broad spectrum of solid malignancies.

As a multi-target agent, catequentinib occupies a distinct niche within the TKI class. Unlike single-target inhibitors such as gefitinib or osimertinib — which are designed around specific oncogenic driver mutations — catequentinib's broader receptor profile makes it applicable to tumor types that lack a single dominant driver alteration. This characteristic has driven its investigation in diseases including lung cancer, osteosarcoma, colorectal cancer, endometrial cancer, and others, frequently in combination with immune checkpoint inhibitors or cytotoxic chemotherapy agents.

Focus of Latest Publications

Recent publications on catequentinib have focused on its use as part of combination regimens across several solid tumors, most often in settings with limited standard options. In glioblastoma, a single-arm phase 2 study evaluated postoperative catequentinib plus radiotherapy in newly diagnosed, unmethylated O6-methylguanine-DNA methyltransferase (MGMT) glioblastoma, a population known to derive minimal benefit from temozolomide-based chemoradiotherapy. The abstract frames this as an effort to improve outcomes with a more effective postoperative strategy.

Several studies examined catequentinib in non-small cell lung cancer and related thoracic malignancies. A prospective single-arm phase II trial assessed tislelizumab plus catequentinib as first-line therapy in advanced pulmonary sarcomatoid carcinoma. Another phase 3 randomized trial compared benmelstobart plus catequentinib with pembrolizumab in previously untreated, driver gene-negative, PD-L1-positive advanced NSCLC. In extensive-stage small cell lung cancer, catequentinib was studied with toripalimab as maintenance therapy after disease control with platinum-etoposide chemotherapy, and the publication also explored a preclinical mechanism involving suppression of neuroendocrine differentiation via Notch1. In addition, a real-world pharmacovigilance analysis using the WHO-VigiAccess database evaluated post-marketing adverse drug reactions for catequentinib alongside gefitinib, afatinib, and osimertinib, noting shared patterns of skin and gastrointestinal toxicity and emphasizing the need for individualized medication choices.

Catequentinib has also been investigated in other refractory or advanced solid tumors. A retrospective study in chemotherapy-refractory osteosarcoma found that catequentinib combined with limb salvage therapy was associated with longer progression-free survival than surgery alone, with manageable adverse reactions. In refractory metastatic colorectal cancer, a phase II single-arm study evaluated catequentinib plus trifluridine-tipiracil as a third-line strategy. A case report described catequentinib plus envafolimab as neoadjuvant therapy in chemotherapy-refractory advanced endometrial cancer, where treatment led to rapid symptom improvement, marked tumor regression, and conversion to surgical candidacy with R0 resection.

Preclinical and translational work has also explored catequentinib-based delivery and mechanism-focused strategies. One study developed a heterogeneous inorganic nanomedicine delivery system loaded with catequentinib for NSCLC, reporting improved tumor targeting, enhanced cytotoxicity, increased reactive oxygen species, modulation of ferroptosis-related proteins, and stronger tumor growth inhibition than free drug in xenograft models. Across these publications, catequentinib is consistently positioned as a multi-target anti-angiogenic agent used in combination with immunotherapy, radiotherapy, chemotherapy, surgery, or nanodelivery approaches to address difficult-to-treat cancers.