pamufetinib (TAS-115) / Otsuka - LARVOL DELTA

AB122 Platform Study (clinicaltrials.gov) - P1 | N=917 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Trial completion date: May 2026 ➔ Jun 2027 | Trial primary completion date: May 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Alveolar Soft Tissue Sarcoma • Biliary Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Antitumor Effects of TAS-115 in Glioblastoma: Evidence from In vitro and In vivo Models (EACR 2026) - "Introduction: Glioblastoma (GBM) is the most aggressive primary brain tumor, with a median survival of 12–15 months despite standard treatment with radiotherapy and temozolomide (TMZ). Our study is of considerable importance in advancing novel therapeutic strategies in the field of GBM and in paving the way for future investigations. The findings further strengthen the potential of TAS-115 as a promising target molecule for subsequent preclinical and translational studies."

Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • KDR • MET

Therapeutic Potential of TAS-115 in Patient-Derived Glioblastoma Models (EACR 2026) - "Temozolomide (TMZ) is a chemotherapeutic agent routinely used in the treatment of patients with GBM. TAS-115 exhibits significant antitumor efficacy in TMZ-sensitive GBM models by inhibiting proliferation, clonogenic growth, migration, and invasion while enhancing apoptotic signaling. These findings support the therapeutic potential of TAS-115 in the treatment of GBM."

Clinical • Brain Cancer • Glioblastoma • Solid Tumor • CASP3 • MET

Pamufetinib (TAS-115) for Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype: A double-blind, multicenter, phase 2b Clinical Trial. (PubMed, Am J Respir Crit Care Med) - "While the safety profile was acceptable, pamufetinib failed to decelerate FVC decline in patients with CF-ILD with a progressive phenotype who had previously been treated with nintedanib or pirfenidone. No benefits were demonstrated by switching from standard antifibrotic treatment to pamufetinib monotherapy.Clinical trial registered with the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/en-top; jRCT2051210050)."

Journal • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Drug-drug interactions with pioglitazone, losartan, and midazolam and anti-tumor efficacy and safety study of TAS-115 in patients with solid tumors. (PubMed, Cancer Chemother Pharmacol) - No abstract available

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

THERAPEUTIC POTENTIAL OF TAS-115 IN 3D BREAST CANCER MODELS. (PubMed, Biofabrication) - "Here, we investigated its therapeutic effects alone and in combination with doxorubicin (DOXO), using 3D heterotypic spheroid models, including free-standing, bioprinted static, and perfused systems. In perfused bioprinted models, TAS-115 markedly inhibited tumor cell migration, highlighting its potential to limit metastatic behavior. These findings identify TAS-115 as a promising therapeutic strategy for TNBC, either as a monotherapy or in combination with chemotherapy."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MET

TAS-115 (Pamufetinib) in Patients With Chronic Fibrosing Interstitial Lung Disease With a Progressive Phenotype: Results of Phase 2b Randomized Clinical Trial (ATS 2025) - "However, TAS-115 did not decelerate FVC decline in patients with CF-ILD with disease progression despite treatment with nintedanib or pirfenidone, compared to the control group. There was no benefit in switching from standard anti-fibrotic treatment to monotherapy with TAS-115."

Clinical • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CSF1R

AB122 Platform Study (clinicaltrials.gov) - P1 | N=715 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | N=367 ➔ 715 | Trial completion date: May 2024 ➔ May 2026 | Trial primary completion date: May 2024 ➔ May 2026

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Alveolar Soft Tissue Sarcoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • KRAS • NRAS

Modulation of tumor immune microenvironment by TAS-115, a multi-receptor tyrosine kinase inhibitor, promotes antitumor immunity and contributes anti-PD-1 antibody therapy. (PubMed, Sci Rep) - "The combination treatment further increased the percentage of GzmbCD8 T cells and decreased the percentage of macrophages compared with either treatment alone. These results highlight the potential therapeutic effect of TAS-115 in combination with PD-1 blockade, mediated via activation of antitumor immunity by TAS-115."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Oncology • Solid Tumor • CSF1R • GZMB • IFNG • IL2

Exploratory phase 2 study of the novel oral multi-kinase inhibitor TAS-115 in patients with idiopathic pulmonary fibrosis. (PubMed, Respir Investig) - "TAS-115 treatment was effective, assessed using intra-patient change in slope of %FVC decline as a surrogate endpoint in patients with IPF pre-treated with pirfenidone or nintedanib and treatment-naïve patients. TAS-115 showed acceptable tolerability and a manageable safety profile."

Journal • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

AB122 Platform Study (clinicaltrials.gov) - P1 | N=292 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | N=180 ➔ 292

Enrollment change • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ALK • BRAF • KRAS • MET • NTRK • RET • ROS1

The K-BASKET trial: A prospective phase II biomarker-driven multiple basket trial in Korean solid cancer patients (ESMO 2019) - "Three treatment arms for the second step are the followings; 1) Patients with MET amplification or exon 14 skipping MET mutation will be assigned to the TAS-115 arm, a novel multikinase inhibitor. 2) Patients with activating PIK3CA or AKT mutations will be assigned to the TAS-117 arm, a novel selective AKT inhibitor...Legal entity responsible for the study: Yonsei University. Funding: National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0018)."

Biomarker • Clinical • IO Biomarker • P2 data • PD(L)-1 Biomarker

Design of phase 2 study of TAS-115, a novel oral multi-kinase inhibitor, in patients with idiopathic pulmonary fibrosis. (PubMed, Contemp Clin Trials Commun) - "This study consists of three cohorts: previously treated with pirfenidone (Cohort P, n = 20), with nintedanib (Cohort N, n = 20), and treatment naïve (Cohort U, n = 10). The safety and tolerability in this population will be assessed. JapicCTI-183898."

Clinical • Journal • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase II, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With Bone Metastases. (PubMed, Clin Genitourin Cancer) - "TAS-115 appears to demonstrate anti-tumor activity and acceptable tolerability in CRPC patients with bone metastases."

Clinical • Journal • P2 data • Genito-urinary Cancer • Hematological Disorders • Oncology • Pain • Prostate Cancer • Renal Disease • Solid Tumor • CSF1R • MET

Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study. (PubMed, Invest New Drugs) - "Conclusion the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013)."

Clinical • Journal • P1 data • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Preclinical evaluation of the multi tyrosine kinase inhibitor TAS-115 in genetically engineered mouse models of prostate cancer (AACR 2018) - "In these studies, TAS-115 showed moderate growth inhibition. Overall our studies show that TAS-115 is capable of suppressing prostate tumor growth by acting primarily on the TME and provide evidence to support further investigation of TME modulation using small molecule multi-kinase inhibitors."

Prostate Cancer

[VIRTUAL] Final Results of the Primary Endpoint and Other Supportive Analysis: TAS-115 Phase 2 Study in Patients with Idiopathic Pulmonary Fibrosis (ATS-I 2020) - "In this phase 2 study, the efficacy of TAS-115 as a single agent was assessed in IPF patients with %FVC decline who had been treated with or were unfit for treatment with Nintedanib or Pirfenidone. TAS-115 as a single agent could be a novel therapeutic agent for IPF and confirmatory trials are currently being planned. JapicCTI-183898"

Clinical • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases

[VIRTUAL] The multi tyrosine kinase inhibitor TAS-115 promotes innate and adaptive immune responses of androgen deprivation therapy in mouse prostate cancer (AACR-II 2020) - "We also use phenotyping, gene expression and immunohistochemical studies to show that reducing immunosuppressive immune cells led to increased CD8 T cell recruitment and activation. These findings provide evidence to support that TAS-115 sequenced with ADT has the potential to augment innate and adaptive antitumor immunity in prostate cancer."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD 163 • CSF1R • IL10 • ITGAM • MET • PTEN • TP53

MET/VEGFR/FMS signaling contributes prostate cancer-induced osteoclast differentiation and bone resorption (AACR 2018) - "These results indicated that administration of TAS-115 restored bone destruction induced by PC3, mainly by inhibiting the FMS-dependent and RANKL-induced differentiation of preosteoclasts into mature osteoclasts. The additional inhibition of the tyrosine kinase FMS by TAS-115 has profound effects on prostate cancer-driven osteoclastogenesis, and its proliferation extends the capability of this agent to act as a powerful antidote to the devastating effects of metastatic spread to bone."

Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

New challenges and inspired answers for anticancer drug discovery and development (Jpn J Clin Oncol) - PMID: 24014883; “Several promising programs are proceeding simultaneously in the clinical or preclinical development stage such as TAS-115, a dual inhibitor of c-Met and vascular endothelial growth factor receptor, TAS-2104, a selective Aurora A inhibitor, TAS-117, an allosteric Akt inhibitor, TAS-2985, an irreversible fibroblast growth factor receptor inhibitor and TAS-2913, a T790M mutant selective epidermal growth factor receptor inhibitor.”

Review • Oncology

MET/VEGFR dual inhibition and prominent safety profile of TAS-115 are favorable for the combination with chemotherapeutic drugs (AACR 2012) - Presentation Time: Monday, Apr 02, 2012, 8:00 AM -12:00 PM; TAS-115 markedly enhanced anti-tumor effect of paclitaxel, & brought tumor shrinkage of approximately 80% in the combination; TAS-115 has disturbed rapid tumor re-growth following paclitaxel treatment

Preclinical-animal • Preclinical-other • Oncology

Final Results of the Primary Endpoint and Other Supportive Analysis: TAS-115 Phase 2 Study in Patients with Idiopathic Pulmonary Fibrosis (ATS 2020) - "In this phase 2 study, the efficacy of TAS-115 as a single agent was assessed in IPF patients with %FVC decline who had been treated with or were unfit for treatment with Nintedanib or Pirfenidone.MethodThe primary analysis was to evaluate the intra-patient change of %FVC between before and after the administration of TAS-115. Those results suggest and support the robustness of the assessment using intra-patients comparison and the proof of concept of TAS-115 for IPF. TAS-115 as a single agent could be a novel therapeutic agent for IPF and confirmatory trials are currently being planned.JapicCTI-183898"

Clinical • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

TAS-115 inhibits PDGFRα/AXL/FLT-3 signaling and suppresses lung metastasis of osteosarcoma. (PubMed, FEBS Open Bio) - "We also show that these signaling pathways are activated in various human osteosarcoma cell lines and are involved in proliferation. Our results suggest that TAS-115 may have potential for development into a novel treatment for metastatic osteosarcoma."

Journal • FLT3

The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-Induced Lung Fibrosis in Mice. (PubMed, Am J Respir Cell Mol Biol) - "Nintedanib, the recently approved multiple kinase inhibitor, has shown promising antifibrotic effects in patients with idiopathic pulmonary fibrosis; however, its efficacy is still limited, and in some cases, treatment discontinuation is necessary owing to toxicities such as gastrointestinal disorders. In a mouse model of bleomycin-induced pulmonary fibrosis, TAS-115 significantly inhibited the development of pulmonary fibrosis and the collagen deposition in bleomycin-treated lungs. These data suggest that the strong inhibition of PDGFR and c-FMS by TAS-115 may be a promising strategy for overcoming the intractable pathogenesis of pulmonary fibrosis."

Journal • Preclinical

Phase I study of TAS-115, a novel oral multi-kinase inhibitor, in patients with advanced solid tumors. (PubMed, Invest New Drugs) - "TAS-115 was generally well tolerated, with manageable toxicities and recommended phase II dose was estimated as 650 mg SID, 5-on/2-off. Furthermore, promising antitumor activity was observed."

Clinical • Journal • P1 data