Atled (fanregratinib) / Hutchmed - LARVOL DELTA

Fanregratinib in fibroblast growth factor receptor 2 (FGFR2)- fusions/rearrangements intrahepatic cholangiocarcinoma (ICC): Pivotal part of a phase II trial (ESMO-GI 2026) - P2/3 | "All pts had received prior chemotherapy (gemcitabine 81.6%, platinum 81.6%, fluorouracil 56.3%) and 72.4% had prior immunotherapy, with 35.6% having ≥ 2 prior lines. No treatment-related deaths occurred. Conclusions F demonstrated promising anti-tumor activity with a manageable safety profile in pretreated FGFR2-fusions/rearrangements ICC, which positions F as a potential new option for this gene-driven population."

P2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

HUTCHMED…announces that the New Drug Application (NDA) for fanregratinib (HMPL-453)…has been granted conditional approval by the China…NMPA for the treatment of adult patients with advanced, metastatic or unresectable intrahepatic cholangiocarcinoma ('ICC') with…FGFR2 fusion or rearrangement who have previously received systemic therapy (GlobeNewswire) - "Fanregratinib will be marketed in China under the brand name ATLED....The approval is supported by data from the Phase II registration cohort of the single-arm, multi-center, open-label, pivotal Phase II/IIIb clinical trial of ATLED in China (NCT04353375)."

China approval • Cholangiocarcinoma

HUTCHMED Highlights Pivotal Phase II Data for Fanregratinib in Intrahepatic Cholangiocarcinoma Presented at ESMO Gastrointestinal Cancers Congress 2026 (GlobeNewswire) - "The study has met its primary endpoint, demonstrating an Independent Review Committee (IRC)-assessed objective response rate (ORR) of 42.5% (95% CI: 30.0%–53.6%). Key secondary endpoints showed consistent clinical activity and a rapid onset of action, with a median time to response of 1.4 months. Median duration of response (DoR) was 6.9 months (95% CI: 5.6–8.5) and disease control rate (DCR) reached 83.9% (95% CI: 74.5%–90.9%). Furthermore, the median progression-free survival (PFS) was 6.9 months (95% CI: 4.1–8.2), while the median overall survival (OS) was 16.6 months (95% CI: 12.4–16.6)."

P2 data • Cholangiocarcinoma

A Phase Ib/II Clinical Study Evaluating HMPL-453 Tartrate as Monotherapy and in Combination With Chemotherapy or Toripalimab in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=190 | Completed | Sponsor: Hutchison Medipharma Limited | Recruiting ➔ Completed | N=141 ➔ 190 | Trial completion date: Aug 2025 ➔ Jan 2026 | Trial primary completion date: Sep 2024 ➔ Jul 2025

Enrollment change • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • FGFR

HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - P2/3 | N=235 | Recruiting | Sponsor: Hutchmed | Phase classification: P2 ➔ P2/3 | N=128 ➔ 235 | Trial completion date: Dec 2025 ➔ Feb 2030 | Trial primary completion date: Jun 2025 ➔ Jun 2028

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2

HUTCHMED Announces NDA Acceptance in China with Priority Review Status for Fanregratinib in Second-Line Intrahepatic Cholangiocarcinoma (HUTCHMED Press release) - "This NDA is supported by data from a single-arm, multi-center, open-label, Phase II registration study in China....Full results will be submitted for presentation at an upcoming scientific conference."

China filing • Priority review • Cholangiocarcinoma

Fanregratinib in China (GlobeNewswire) - "Recruitment for the registrational Phase II study in patients with advanced intrahepatic cholangiocarcinoma (IHCC) in China has been completed, with new drug application submission preparation underway for the first half of 2026."

China filing • Cholangiocarcinoma

HUTCHMED Announces that it has Completed Enrollment of a Phase II Registration Study of Fanregratinib (HMPL-453) for Intrahepatic Cholangiocarcinoma in China (GlobeNewswire) - "HUTCHMED...announces that it has completed enrollment of its a Phase II trial of fanregratinib (HMPL-453) for intrahepatic cholangiocarcinoma ('IHCC') patients with fibroblast growth factor receptor ('FGFR')2 fusion/rearrangement....A total of 87 patients were enrolled into the registration phase of the study....The first patient received the first dose in March 2023 and HUTCHMED expects to announce topline results from the study around the end of 2025. If favorable, the results could enable a New Drug Application submission to China’s National Medical Products Administration (NMPA)."

P2 data • Trial status • Cholangiocarcinoma

HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Hutchmed | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Aug 2023

Trial completion • Trial completion date • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase 2 Study of HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - P2 | N=128 | Recruiting | Sponsor: Hutchmed | Not yet recruiting ➔ Recruiting | N=29 ➔ 128 | Trial completion date: Jun 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Jun 2025

Enrollment change • Enrollment open • Metastases • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • FGFR2

HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Hutchmed

New P1 trial • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A phase 2 study of HMPL-453, a selective FGFR tyrosine kinase inhibitor (TKI), in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions. (ASCO 2023) - P2 | "All pts had received ≥1 prior treatment line and 21 (84%) had received previous gemcitabine-based chemotherapy. HMPL-453 showed promising efficacy, particularly in RP2D regimen (300 mg, QD, 2w on/1w off) and acceptable toxicity in pts with previously-treated advanced iCCA and FGFR fusions. These results warrant further study in pts with advanced iCCA. Clinical trial information: NCT04353375."

Clinical • Metastases • P2 data • Biliary Cancer • Cholangiocarcinoma • Dermatology • Gastrointestinal Cancer • Oncology • Solid Tumor • Xerostomia • FGFR1 • FGFR2

HUTCHMED Highlights Presentations at the 2023 ASCO Annual Meeting (GlobeNewswire) - "HUTCHMED (China) Limited...announces that new and updated clinical data...will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting....Here we present first-in-human data for HMPL-453 in patients with previously treated advanced intrahepatic cholangiocarcinoma (IHCC) harboring FGFR2 fusions. A Phase II registration intent cohort is currently enrolling such patients (NCT04353375)."

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

HMPL-453, a highly selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays potent activity in FGFR-altered tumor models (AACR 2023) - P2 | "HMPL-453 is a highly potent and selective inhibitor of FGFR 1, 2, and 3 with strong activity against FGFR-deregulated tumors in preclinical models, supporting continued investigation in patients with FGFR alterations (such as fusion and mutation) either as a single agent or in combination with PD-1 blockade."

IO biomarker • Preclinical • Oncology • FGFR • FGFR2 • FGFR4

HUTCHMED Initiates Registration Phase Enrollments of HMPL-453 for IHCC and Savolitinib for Gastric Cancer following NMPA Consultations (GlobeNewswire) - "HUTCHMED (China) Limited...announces that it has consulted the China National Medical Products Administration ('NMPA') and reached an agreement to initiate the registration phase of the ongoing Phase II trial of HMPL-453 for intrahepatic cholangiocarcinoma ('IHCC') patients with fibroblast growth factor receptors ('FGFR') 2 fusion. If positive, the data from the registration phase may be used to support a future New Drug Application ('NDA') filing. The first patient received their first dose in March 2023. In addition, it also reached an agreement to initiate the registration phase of the ongoing Phase II trial of savolitinib for gastric cancer patients with mesenchymal–epithelial transition ('MET') amplification following NMPA consultation. If positive, the data from the registration phase may be used to support a future NDA filing. The first patient also received their first dose in March 2023."

Trial status • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR • MET

HUTCHMED Highlights Presentations at American Association for Cancer Research Annual Meeting 2023 (GlobeNewswire) - "HUTCHMED (China) Limited...announces that new and updated clinical and non-clinical data related to five HUTCHMED investigational drug candidates will be presented during the American Association for Cancer Research Annual Meeting 2023 (AACR 2023)....HMPL-453:...The presentation outlines preclinical data that shows that HMPL-453 is a highly potent and selective inhibitor of FGFR 1, 2, and 3 with strong activity against FGFR-deregulated tumors in preclinical models, supporting continued investigation in patients with FGFR alterations (such as fusion and mutation) either as a single agent or in combination with PD-1 blockade."

Preclinical • Oncology • FGFR • FGFR1 • FGFR2 • FGFR3

Chi-Med reports 2019 full year results and provides updates on key clinical programs (GlobeNewswire) - "KEY EVENTS PLANNED FOR 2020...Early 2020: Savolitinib – Phase Ib/II data (CALYPSO) – PRCC cohort overall survival results for the Imfinzi® / savolitinib combination presented at ASCO GU (February 2020); HMPL-453 – Phase II study start – FGFR 1/2/3 inhibitor in advanced malignant mesothelioma; Savolitinib – NDA submission in MET exon 14 deletion NSCLC in China – first NDA submission globally for savolitinib; Surufatinib – NDA submission in pancreatic NET in China – following the recent positive SANET-p Phase III interim analysis."

Non-US regulatory • P1/2 data • Trial status • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma

HMPL-453 (FGFR Inhibitor) in Combination With Chemotherapy or Anti-PD-1 Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=141 | Recruiting | Sponsor: Hutchison Medipharma Limited | Not yet recruiting ➔ Recruiting | Trial primary completion date: Mar 2024 ➔ Sep 2024

Combination therapy • Enrollment open • IO biomarker • Trial primary completion date • Oncology • Solid Tumor • FGFR

HUTCHMED Initiates Phase Ib/II Study of HMPL-453 in Combination with Chemotherapy or Toripalimab for Advanced Solid Tumors in China (GlobeNewswire) - "HUTCHMED (China) Limited...today announces that it has initiated a Phase Ib/II study in China of HMPL-453, an investigational novel selective inhibitor targeting fibroblast growth factor receptors ('FGFR') 1/2/3, in combination with chemotherapy or the anti-PD-1 therapy, toripalimab. The first patient received their first dose on January 22, 2022...A Phase II study of HMPL-453 monotherapy is also underway in patients with advanced intrahepatic cholangiocarcinoma (IHCC) in China..."

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

HMPL-453 Tartrate Combined With Chemotherapy or Teriprizumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=141; Not yet recruiting; Sponsor: Hutchison Medipharma Limited

Clinical • New P1/2 trial • Cholangiocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CTLA4 • FGFR2

HUTCHMED Reports 2021 Interim Results and Provides Business Updates (GlobeNewswire) - “Potential upcoming clinical and regulatory milestones for HMPL-523: Initiate dose expansion of the Phase I study (NCT03779113) in the U.S. and Europe, following completion of dose escalation, in the second half of 2021; Potential upcoming clinical and regulatory milestones for HMPL-453: Initiate studies in combination with other anti-cancer therapies in China in late 2021 or early 2022, based on the response to the late June 2021 submission of an IND to the NMPA."

New trial • Trial status • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Chi-Med Initiates a Phase II Trial of HMPL-453 in Patients with Advanced Intrahepatic Cholangiocarcinoma in China (GlobeNewswire) - "Hutchison China MediTech...has initiated a Phase II study of HMPL-453, its novel small molecule inhibitor targeting fibroblast growth factor receptors ('FGFR'), in patients with advanced intrahepatic cholangiocarcinoma ('IHCC'), which is a type of liver cancer. The clinical study is a single-arm, multi-center, open-label study, evaluating the efficacy, safety and pharmacokinetics of HMPL-453 in patients with advanced IHCC with FGFR2 fusion that had failed at least one line of systemic therapy. The primary outcome measure is objective response rate (ORR)."

Trial status • Cholangiocarcinoma • Oncology

HMPL-453 in Advanced Malignant Mesothelioma (clinicaltrials.gov) - P2; N=27; Recruiting; Sponsor: Hutchison Medipharma Limited; Not yet recruiting ➔ Recruiting; Initiation date: Mar 2020 ➔ Dec 2019

Clinical • Enrollment open • Trial initiation date • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • Thoracic Cancer • FGFR

Phase II Study of HMPL-453 Tartrate in Patients With Advanced Intrahepatic Cholangiocarcinoma With FGFR2 Fusion (clinicaltrials.gov) - P2; N=29; Not yet recruiting; Sponsor: Hutchison Medipharma Limited

Clinical • New P2 trial • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Chi-Med initiates a phase II trial of HMPL-453 in patients with advanced malignant mesothelioma in China (Hutchison China MediTech Press release) - "Hutchison China MediTech Limited...has initiated a Phase II study of HMPL-453, its novel small molecule inhibitor targeting fibroblast growth factor receptors ('FGFR'), in patients with advanced malignant mesothelioma. The clinical study is a single-arm, multi-center, open-label study, evaluating the efficacy, safety and pharmacokinetics of HMPL-453 in historically confirmed patients with advanced malignant mesothelioma that failed at least one line of systemic therapy. The primary outcome measure is overall response rate (ORR)."

Trial initiation date