ArticleCancer medicine2021
Phase 1b study of galunisertib and ramucirumab in patients with advanced hepatocellular carcinoma.
Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- HBV reprograms the tumor microenvironment in hepatocellular carcinoma: mechanisms and therapeutic implications.Clinical and experimental medicine · 2026Review
- Mechanisms and therapeutic strategies of bidirectional crosstalk between hepatic stellate cell-derived cancer-associated fibroblasts and T cells in immune evasion and therapeutic resistance of hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib.Journal of clinical medicine · 2025Review
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- Emerging Immunotherapy Targets in Early Drug Development.International journal of molecular sciences · 2025Review
- The fibroinflammatory response in cancer.Nature reviews. Cancer · 2025Review
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches.Cancers · 2025Review
- NPC1 controls TGFBR1 stability in a cholesterol transport-independent manner and promotes hepatocellular carcinoma progression.Nature communications · 2025Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Traditional Chinese Medicine targeting the TGF-β/Smad signaling pathway as a potential therapeutic strategy for renal fibrosis.Frontiers in pharmacology · 2025Review
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Galunisertib promotes bevacizumab-induced vascular normalization in nasopharyngeal carcinoma: Multi-parameter MRI evaluation.Molecular therapy. Oncology · 2024Article
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
- Small-molecule agents for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Review
- TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo.Nature communications · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPreclinical data suggest that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β signaling interact to stimulate angiogenesis and suppress antitumor immune responses. Thus, combined inhibition of both pathways may offer greater antitumor activity compared with VEGF-targeted antiangiogenic monotherapy against hepatocellular carcinoma (HCC).
methodsThis is a multicenter, open-label, phase 1b study of galunisertib, an inhibitor of TGF-β receptor 1, and ramucirumab, an anti-VEGF receptor 2 antibody, in patients with advanced HCC aiming to define the maximum tolerated dose (MTD). Secondary objectives included safety, pharmacokinetics (PK), antitumor efficacy, and plasma alpha-fetoprotein and TGF-β kinetics. Dose escalation employed a 3 + 3 design. Patients received galunisertib at 80 mg (cohort 1) or 150 mg (cohort 2) orally twice a day on days 1-14 of a 28-day cycle combined with ramucirumab 8 mg/kg intravenously every 2 weeks.
resultsEight patients were enrolled: three in cohort 1 and five in cohort 2 (two patients were unevaluable due to rapid disease progression and replaced). No dose-limiting toxicities were observed. Treatment-related adverse events (AEs) of any grade in ≥2 patients included nausea (25%) and vomiting (25%). There was one Grade 3 treatment-related AE, a cerebrovascular accident possibly related to ramucirumab. Galunisertib exposure was dose-proportional and not affected by ramucirumab. The RECIST version 1.1 objective response rate and disease control rate were 0% and 12.5%, respectively.
conclusionCombination therapy was safe and tolerable and displayed favorable PK. The MTD was established at galunisertib at 150 mg orally twice a day and ramucirumab 8 mg/kg intravenously every 2 weeks. The results do not support the preclinical hypothesis that blocking TGFβ signaling enhances efficacy of VEGF-targeted therapy; thus further clinical development was halted for the combination of galunisertib and ramucirumab.
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