tinengotinib (TT-00420) / TransThera Biosci - LARVOL DELTA

Phase II study of tinengotinib in advanced cholangiocarcinoma: Analysis of molecular response and resistance mechanisms. (ASCO-GI 2026) - P2 | "Funded by TransThera Sciences (Nanjing), Inc. Clinical Trial Registration Number: NCT04919642 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Metastases • P2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Targeting high-risk MYC-overexpressed osteosarcoma with an Aurora kinase inhibitor:--results from a pilot umbrella trial. (PubMed, NPJ Precis Oncol) - P=N/A | "Patients were assigned to three arms: (A) PD-1 antibody plus gemcitabine and docetaxel; (B) PARP inhibitor combined with temozolomide; or (C) tinengotinib (TT-00420), a small-molecule aurora kinase inhibitor currently in clinical trials. This study demonstrated the feasibility of using genomic molecular subtyping to guide the precise treatment of osteosarcoma. We also revealed that the abnormal genomic and transcriptomic profiles caused by MYC amplification could be suppressed by tinengotinib."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • HRD • MYC

Tinengotinib for adults with advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 trial. (PubMed, Lancet Gastroenterol Hepatol) - P2 | "These findings suggest that tinengotinib might have activity in patients with cholangiocarcinoma with FGFR2 fusions that progressed following FGFR inhibitor therapy. Anti-tumour activity was also observed in patients with other FGFR alterations. The data from this phase 2 study supported the initiation of a phase 3 registration trial."

Journal • P2 data • Biliary Cancer • Cardiovascular • Cholangiocarcinoma • CNS Disorders • Dental Disorders • Dermatology • Hypertension • Oncology • Solid Tumor • Stomatitis • FGFR2

Inclusion of tinengotinib tablets in the list of products for priority review by the national medical products administration (The Manila Times) - "TransThera Sciences Nanjing, Inc. (the 'TransThera') announced that Tinengotinib tablets have been included in the List of Products for Priority Review by the Center for Drug Evaluation ('CDE') of the National Medical Products Administration ('NMPA') of the PRC, with the proposed indication for the treatment of adults with unresectable advanced or metastatic cholangiocarcinoma (CCA) who have received at least one prior systemic treatment and FGFR inhibitor treatment."

China filing • Priority review • Cholangiocarcinoma

TransThera Publishes Clinical Studies of Tinengotinib (TT-00420) against Cholangiocarcinoma on Lancet (PRNewswire) - "In a multicenter, open-label Phase 2 trial (NCT04919642), patients with FGFR2 fusion-positive CCA who had either primary resistance or developed acquired resistance to prior FGFR inhibitor (FGFRi) therapy were enrolled, along with patients harboring other FGFR alterations or FGFR wiled-type tumors. Tinengotinib demonstrated clinical activity in patients with FGFR2 fusion-positive CCA with acquired FGFRi resistance, as well as in those with other FGFR-altered subtypes."

P2 data • Cholangiocarcinoma

Tinengotinib in advanced or metastatic HR+/HER2- and TNBC: efficacy and biomarker correlative analysis from a phase Ib/II study (SABCS 2025) - P1/2 | "Tinengotinib exhibited promising clinical benefit and manageable safety profile for the treatment of HR+/HER2- BC or TNBC. The biomarker correlative analysis revealed that ROS1 mutations could be a potential predictive biomarker. Early reduction in ctDNA VAF may serve as a pharmacodynamic biomarker."

Biomarker • Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • CDKN2A • CSF1R • CTNNA1 • DNMT3A • ERBB3 • FGFR2 • HER-2 • JAK1 • JAK2 • KMT2D • MLL2 • NF1 • PDGFRB • PIK3CA • PTEN • RAD51D • ROS1 • TP53

Survival and safety of tinengotinib in pooled patients with advanced, fibroblast growth factor receptor (FGFR) inhibitor refractory/relapsed cholangiocarcinoma (CCA) (ESMO 2025) - P1, P1/2, P2 | "Conclusions Tinengotinib shows promising efficacy with an acceptable safety profile in CCA pts with notable clinical benefit in FGFR2-altered CCA with prior FGFRi(s). A global phase III study is currently open to further assess the efficacy and safety of tinengotinib in FGFR2-altered CCA pts who progressed on chemotherapy and FGFRi."

Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR • FGFR2

Unravelling Tinengotinib's Mechanistic Landscape in Triple-Negative Breast Cancer Via Network Pharmacology and in Silico Simulation Techniques. (PubMed, Cell Biochem Biophys) - No abstract available

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

VOLUNTARY ANNOUNCEMENT (HKEXnews) - "The board of directors of the Company...is pleased to announce that the phase II clinical trial of the Company’s core product Tinengotinib (TT-00420) in combination with Fulvestrant for the treatment of previously treated hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative or low expression (HER2-) relapsed or metastatic breast cancer has obtained Investigational New Drug (IND) approval from the National Medical Products Administration (NMPA) of the PRC on September 10, 2025."

New P2 trial • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

FIRST PATIENT DOSED IN PHASE II CLINICAL TRIAL OF TINENGOTINIB IN COMBINATION WITH AKESO’S (CADONILIMAB, PD-1/CTLA-4) / (IVONESCIMAB, PD-1/VEGF) (HKEXnews) - "This trial is an open-label, multicenter Phase II clinical study conducted in China to evaluate the efficacy and safety of (cadonilimab, PD-1/CTLA-4)/(ivonescimab, PD-1/ VEGF) in combination with Tinengotinib tablets for the treatment of advanced HCC."

Trial status • Hepatocellular Cancer

Study of TT-00420 (Tinengotinib) in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Chemotherapy and FGFR Inhibitor (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: TransThera Sciences (Nanjing), Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2

Safety of TT-00420 (Tinengotinib) Monotherapy in Patients With Advanced Solid Tumors and Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: TransThera Sciences (Nanjing), Inc. | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

A Phase II Clinical Study of AK104/AK112 in Combination With TT-00420 Tablet for Advanced HCC. (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Akeso

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Tinengotinib (TT-00420) inhibits tumor growth and overcomes multidrug resistance in gastrointestinal cancers (IDDF 2025) - "Additionally, trastuzumab-resistant and immunotherapy-resistant models were established to evaluate TT-00420's potential in overcoming drug resistance. Western blot analysis confirmed that Aurora A played a crucial role in mediating its tumor-suppressive effects in resistant models.Conclusions TT-00420 is a highly promising anti-tumor agent, exhibiting potent efficacy against CRC and GC. Our findings provide a new therapeutic approach for gastrointestinal cancers and offer valuable insights for future clinical research."

Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • FGFR • HER-2 • PD-1

TransThera Publishes Translational Studies of Tinengotinib (TT-00420) against Cholangiocarcinoma on Annals of Oncology (The Manila Times) - "The article discloses for the first time the co-crystal structure of tinengotinib with the FGFR2 kinase domain of its unique binding mode, in addition to kinetic studies to illustrate its higher affinity compared to first-generation FGFR inhibitors, in vitro and in vivo activities against clinically acquired FGFR2 resistance mutations, as well as a case report to demonstrate its clinical efficacy."

Preclinical • Cholangiocarcinoma

GRANT OF TINENGOTINIB (TT-00420) FAST TRACK DESIGNATION FOR TREATMENT OF MCRPC (HKEXnews) - "The board of directors of the Company (the 'Board') is pleased to announce that the U.S. Food and Drug Administration (the 'FDA') has granted the fast track designation of tinengotinib for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC)....In the phase I/II studies of tinengotinib monotherapy, 13 mCRPC patients with measurable disease were enrolled. The overall response rate (ORR) was 46%, and the disease control rate (DCR) was 85%."

Fast track • Castration-Resistant Prostate Cancer

To Evaluate Efficacy and Safety of TT-00420 (Tinengotinib) as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=84 | Completed | Sponsor: TransThera Sciences (Nanjing), Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Aug 2024

Monotherapy • Trial completion • Trial completion date • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Endocrine Cancer • Gallbladder Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • HER-2

Use of an in-silico clinical trial intelligence solution to predict outcomes of tinengotinib, a potent multi-kinase small molecule FGFR inhibitor in patients with cholangiocarcinoma, based on the molecular matching score. (ASCO 2025) - P2 | "The CureMatch Matching Score significantly correlated with outcomes for tinengotinib, a potent FGFR inhibitor given to patients with cholangiocarcinoma, with activity in both FGFR-altered and FGFR wild-type patients. Additional studies of this algorithmic Matching Score's ability to predict outcome and therefore optimize treatment for a variety of pharmaceutical agents are warranted."

Biomarker • Clinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2

Correlation of clinical and biomarker data in FGFR inhibitor failed metastatic cholangiocarcinoma patients with tumor response to tinengotinib (AACR 2025) - P1/2, P3 | "Both pts were previously treated with chemotherapy and pemigatinib. An inverse correlation between the presence of KD mutations and the response to tinengotinib treatment was observed in these two FGFRi relapsed/refractory metastatic CCA pts. This suggests tinengotinib may overcome acquired resistance to FGFRi in CCA pts. An ongoing randomized phase III study is investigating tinengotinib vs."

Biomarker • Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2

The multi-kinase inhibitor tinengotinib as a novel therapy for advanced prostate cancer (AACR 2025) - "Small molecule inhibition was used to assess the role of tinengotinib targets in driving cancer cell survival and growth. Tinengotinib potently inhibited growth of all cell lines, including enzalutamide-sensitive and -resistant AR signaling-dependent models (LNCaP, LNCaP95, LNCaP-XER), double negative models (PC-3) and neuroendocrine-like (LASPC-01) lineages, with IC50s ranging from low nanomolar to ~1 μM. Preclinical evaluation of tinengotinib shows efficacy across a range of prostate cancer phenotypes and combined effectively with standard agents. Gene expression across this panel of cell lines pinpoints Aurora A and B, JAK2, and FGFR3 as potential mechanisms of action for tinengotinib in prostate cancer. Future studies are aimed at understanding its mechanisms of action and determining its potential as a combination therapy for mCRPC."

Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AURKA • FGFR1 • FGFR3 • FLT1 • JAK1 • JAK2 • STAT3

Safety and pharmacokinetics of tinengotinib monotherapy in different doses and dosing schedules in advanced solid tumors (AACR 2025) - P1/2 | "There were no discernable trends in safety or PK between the BID and QD dose schedules. Although there was an increase in TRAEs with overall dose increase, the 10mg QD dose was shown to have an optimal PK profile and demonstrated superior efficacy as compared to the other dose levels. These results suggest that the combination of known PK and safety predictability with promising efficacy provides a basis of dose selection for further clinical development of tinengotinib.Clinical trial Information: NCT04742959"

Clinical • Metastases • Monotherapy • PK/PD data • Oncology • Solid Tumor

A phase 1b/2 study evaluating the activity of tinengotinib in combination with androgen receptor pathway inhibitors (ARPIs) in patients with metastatic castration resistant prostate cancer (mCRPC). (ASCO-GU 2025) - P1/2 | " This is a multi-center, phase 1b/2 study of tinengotinib plus either abiraterone/prednisone or enzalutamide in patients with mCRPC. As of October 2024, 2 patients have been enrolled in phase 1b across 1 site. Enrollment for phase 2 is expected to begin in January 2025."

Clinical • Combination therapy • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FGFR • JAK1

Tinengotinib in patients with advanced, metastatic cholangiocarcinoma: Overall survival results and biomarker correlative analysis from a phase 2 clinical trial. (ASCO-GI 2025) - P2, P3 | "Tinengotinib has shown promising anti-tumor efficacy in CCA pts with FGFR fusion after prior FGFRi and in those with primary FGFR mutations. An ongoing randomized phase III study will investigate tinengotinib vs. chemotherapy in FGFR inhibitor refractory CCA (NCT05948475)."

Biomarker • Clinical • Metastases • P2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • ARID1A • BCOR • FGFR2 • MED12

Multiple Kinase Small Molecule Inhibitor Tinengotinib (TT-00420) Alone or With Chemotherapy Inhibit the Growth of SCLC. (PubMed, Cancer Sci) - "When combined with etoposide/cisplatin, it synergistically inhibited SCLC growth. Mechanistic studies revealed that c-Myc expression may be a key factor influencing the effect of tinengotinib in SCLC-N. This study provides reliable preclinical data and a new direction for tinengotinib as a promising therapy for SCLC, either alone or in combination with chemotherapy."

Journal • Lung Cancer • Oncology • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • MYC • NEUROD1

A Model for Decoding Resistance in Precision Oncology: Acquired Resistance to FGFR inhibitors in Cholangiocarcinoma. (PubMed, Ann Oncol) - "Our multimodal analysis led to a model characterizing the biology of acquired resistance, informing the rational design of next-generation FGFR inhibitors. FGFR inhibitors should be small, high-affinity, and selective for specific FGFR family members. Tinengotinib, a novel small molecule inhibitor with these characteristics, exhibited preclinical and clinical activity against key resistance mutations. This integrated approach offers a blueprint for advancing drug resistance research across cancer types."

Journal • Preclinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2