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

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

2024 ESMO Asia: TransThera announces clinical data of tinengotinib in combination with atezolizumab (PD-L1) in biliary tract carcinoma (BTC) (PRNewswire) - P1b/2 | N=114 | NCT05253053 | "A total of 20 intrahepatic cholangiocarcinoma patients were efficacy evaluable. The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 80.0%, the median progression free survival (mPFS) reached 8.77 months and the 12-month overall survival (OS) rate was 70.1%; A total of 28 cholangiocarcinoma patients were efficacy evaluable. The ORR and DCR were 25.0% and 75.0%, the mPFS reached 5.72 months and the 12-month OS rate was 64.8%; All 31 BTC patients were efficacy evaluable. The ORR and DCR were 22.6% and 74.2%, the mPFS reached 4.11 months and the 12-month OS rate was 61.8%; No DLT was observed in the dose escalation phase; The combination therapy was generally well tolerated in heavily pre-treated BTC patients."

P1/2 data • Biliary Tract Cancer

Tinengotinib (TT-00420) in combination with atezolizumab (atezo) in Chinese patients (pts) with biliary tract carcinoma (BTC): Efficacy and safety results from a phase Ib/II study (ESMO Asia 2024) - P1/2 | "Conclusions TT combined with atezo has promising antitumor activities and well-tolerated safety profiles in heavily pre-treated BTC pts. The results support a further study to evaluate the safety and efficacy of TT plus ICI in BTC pts who had prior ICI and/or chemotherapy."

Clinical • Combination therapy • P1/2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR • PD-L1

TARGETING HIGH RISK MYC- AMPLIFIED OSTEOSARCOMA BY AURORA KINASE INHIBITOR--RESULT FROM A NGS BASED UMBRELLA TRIAL (CTOS 2024) - P=N/A, P2, P4 | "Patients with MYC amplification are very aggressive and have an extremely poor prognosis. TT-00420 depicted robust anti-tumor activity in Myc-amplified OS both in vitro and in vivo with downregulation of c-Myc expression, indicating its potential as active drug for OS patients with c-Myc amplification. In addition, TT-00420 may increase the immune infiltration in microenvironment and enhance efficacy of PD-1 immunotherapy."

IO biomarker • Next-generation sequencing • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • MYC

TransThera Announces the Global Multicenter Phase 3 Clinical Trial Completed First Patient Dosing in the US Evaluating Tinengotinib in FGFRi Relapsed/Refractory Patients with Cholangiocarcinoma (PRNewswire) - "TransThera...today announces the first patient has been dosed in the US for the Phase 3 trial FIRST-308 of tinengotinib (TT-00420), an investigational next generation FGFR inhibitor to treat advanced FGFR-altered cholangiocarcinoma（CCA）patients who had progressed on prior systemic therapy and FGFR inhibitors....This study is a Phase 3, randomized, controlled, global multicenter study to evaluate the efficacy and safety of oral tinengotinib versus physician's choice in subjects with FGFR-altered, chemotherapy- and FGFR Inhibitor-refractory/relapsed cholangiocarcinoma. The study is planned to be conducted in the US, the EU, the UK, Asia, and other countries and regions, and the final results will support a global marketing application for tinengotinib....In July 2023, tinengotinib was granted the Breakthrough Therapy Designation (BTD) by NMPA in China."

Breakthrough therapy • Trial status • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Pharmacokinetics, Mass Balance, and Biotransformation of [14C]tinengotinib, A Novel Multi-target Kinase Inhibitor, in Healthy Subjects. (PubMed, Drugs R D) - "Overall, tinengotinib demonstrated a complete mass balance with limited renal excretion, no disproportionate blood metabolism, and slow elimination, primarily through the fecal route. The results of this study provide evidence to support the rational use of tinengotinib as a pharmacotherapeutic agent."

Journal • PK/PD data • CYP3A4

Yaojie Ankang lost nearly 600 million in two years: the cost of clinical trials without commercialization has increased significantly, and the initial effect may be seen in 2025 [Google translation] (163.com) - "Most core product trials are concentrated in 2025...The purpose of fundraising shows that approximately 61.0% will be allocated to fund the research and development of the core product Tinengotinib....10.4% will be used to fund the ongoing Phase Ib/II clinical trial of Tinengotinib combined with atezolizumab for the treatment of cholangiocarcinoma in China, and to fund the Phase II/III clinical trial of Tinengotinib combined with immunotherapy for the treatment of cholangiocarcinoma. The Phase Ib/II clinical trial is expected to be completed in the fourth quarter of 2024, and the Phase II/III clinical trial will start in 2025."

Financing • New P2/3 trial • Trial completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Yaojie Ankang lost nearly 600 million in two years: the cost of clinical trials without commercialization has increased significantly, and the initial effect may be seen in 2025 [Google translation] (163.com) - "The purpose of fundraising shows that approximately 61.0% will be allocated to fund the research and development of the core product Tinengotinib....Of this, 7.9% will be used to fund the ongoing pivotal Phase II clinical trial of Tinengotinib monotherapy for the treatment of cholangiocarcinoma in China, which is expected to be completed in the second half of 2025; 36.9% will be used to fund the ongoing multi-regional registration Phase III clinical trial of Tinengotinib monotherapy for the treatment of cholangiocarcinoma, which is expected to complete patient enrollment in the second half of 2026; 5.8% will be used to fund the planned Phase II clinical trial of Tinengotinib combined with NHT for the treatment of mCRPC in China, which is expected to start in the first half of 2025."

Enrollment status • Financing • New P2 trial • Trial completion date • Castration-Resistant Prostate Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Solid Tumor

Yaojie Ankang went public in Hong Kong, but still has no commercial products and has suffered losses of nearly 600 million yuan in two years [Google translation] (new.qq.com) - "Glodon learned that recently, Yaojie Ankang (Nanjing) Technology Co., Ltd...submitted a prospectus to the Hong Kong Stock Exchange and plans to be listed on the main board of Hong Kong . CITIC Securities and Huatai International are the joint sponsors...In this IPO, Yaojie Ankang plans to use the funds raised to fund the research and development of the company's core product Tinengotinib; to fund the research and development of other pipeline products; and for general operating capital and general corporate purposes....According to the prospectus, the company has completed nine rounds of financing, with a total financing amount of more than 1.7 billion yuan."

Financing • Biliary Tract Cancer • Breast Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Yaojie Ankang submitted its application to the Hong Kong Stock Exchange for the second time: There is no commercial product yet, and the accumulated loss is 1.125 billion yuan. The market space for core products may be limited [Google translation] (Sina Corp) - "Among the 7 product pipelines, Tinengotinib (TT-00420) is Yaojie Ankang's core product and the pipeline closest to commercialization...Between 2022 and 2023, Yaojie Ankang's R&D expenditures were 263 million yuan and 344 million yuan respectively. Among them, the R&D expenses for the core product Tinengotinib were 167 million yuan and 236 million yuan respectively, which is the bulk of the company's R&D expenditures. As of June 20, 2024, Tinengotinib has a total of 8 clinical trials being conducted simultaneously. Among them, the indication of single-drug use for cholangiocarcinoma is undergoing Phase III international multicenter clinical trials in the United States, South Korea, the United Kingdom, the European Union and other places, and the indication of single-drug use for cholangiocarcinoma is undergoing Phase II pivotal clinical trials in China."

Commercial • Trial status • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of Tinengotinib (TT-00420) in Combination With Standard Treatments in People With Prostate Cancer (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Combination therapy • Metastases • New P1/2 trial • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Study of TT-00420 (Tinengotinib) Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=203 | Completed | Sponsor: TransThera Sciences (Nanjing), Inc. | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endocrine Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Lung Cancer • Oncology • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • FGFR

Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma (clinicaltrials.gov) - P2 | N=55 | Completed | Sponsor: TransThera Sciences (Nanjing), Inc. | Active, not recruiting ➔ Completed

Metastases • Trial completion • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR • FGFR2

Rollover Study to Provide Continued Access to TT-00420 (Tinengotinib) for Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: TransThera Sciences (Nanjing), Inc.

Metastases • Monotherapy • New trial • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Tinengotinib in patients with advanced solid tumors harboring actionable FGFR1-3 mutations (AACR 2024) - P1, P1/2, P2 | "We observed promising clinical benefit with tinengotinib in heavily pretreated solid tumor pts with FGFR1-3 mutations. The side effects profile was manageable and no new safety signals have been identified. Further research is planned to evaluate the safety and efficacy of tinengotinib in pts with FGFR1-3 mutations across a wider variety of tumor types."

Clinical • Late-breaking abstract • Metastases • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Leiomyosarcoma • Oncology • Pancreatic Cancer • Prostate Cancer • Sarcoma • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3

【2024 AACR Late Breaking Research】TransThera announces clinical data of tinengotinib to treat patients with advanced solid tumors harboring actionable FGFR1-3 alterations (PRNewswire) - "TransThera Sciences...announced the poster presentation at the 2024 American Association for Cancer Research (AACR) to discuss the latest breaking research of tinengotinib for patients with advanced solid tumors harboring actionable FGFR1-3 alterations...The retrospective analysis of the pooled results from four clinical studies of tinengotinib in advanced solid tumors harboring actionable FGFR1-3 mutations showed efficacy in multiple tumor types, including cholangiocarcinoma, breast, prostate, urothelium, colon and head and neck cancer. Our data demonstrate 33.3% BOR and 88.2% DCR, 6.90 months mPFS. The promising results validated the novel mechanism of tinengotinib and clinical applications for potentially FGFR 1-3 altered patients with solid tumors."

Late-breaking abstract • Retrospective data • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

[2024 AACR Late Breaking Research] TransThera announces clinical data of tinengotinib to treat patients with advanced solid tumors harboring actionable FGFR1-3 alterations (PRNewswire) - "The retrospective analysis of the pooled results from four clinical studies of tinengotinib in advanced solid tumors harboring actionable FGFR1-3 mutations showed efficacy in multiple tumor types, including cholangiocarcinoma, breast, prostate, urothelium, colon and head and neck cancer. Our data demonstrate 33.3% BOR and 88.2% DCR, 6.90 months mPFS. The promising results validated the novel mechanism of tinengotinib and clinical applications for potentially FGFR 1-3 altered patients with solid tumors."

Retrospective data • Breast Cancer • Cholangiocarcinoma • Colon Cancer • Genito-urinary Cancer • Head and Neck Cancer • Prostate Cancer • Solid Tumor • Urothelial Cancer