On September 3, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that it 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 (Press release, Hutchison China MediTech, SEP 3, 2020, https://www.chi-med.com/chi-med-initiates-a-phase-ii-trial-of-hmpl-453-in-patients-with-advanced-ihcc-in-china/ [SID1234564383]).
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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). Secondary outcome evaluations include preliminary efficacy measures, such as disease control rate (DCR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Additional details may be found at clinicaltrials.gov, using identifier NCT04353375.
About IHCC
IHCC is a cancer that develops in the cells within the bile ducts[1]. With over 390,000 new cases every year, China accounted almost 50% of the world’s annual incidence of liver cancer in 2018.[2],[3] After hepatocellular carcinoma ("HCC"), IHCC is the second most common primary hepatic malignancy accounting for 10% to 20% of newly diagnosed liver cancers[4]. Approximately 10-15% of IHCC patients have tumors that harbor FGFR2 fusion[5],[6]. Long-term survival for patients with IHCC is worse than for HCC, which may be related to a high propensity for regional and distant metastases as well as the lack of effective systemic therapy options[4].
About FGFR
FGFRs are a sub‑family of receptor tyrosine kinases. Activation of FGFR signaling pathways is central to several biological processes. In normal physiology, FGF/FGFR signaling is involved in embryonic development (organogenesis and morphogenesis), tissue repair, angiogenesis, neuroendocrine and metabolism homeostasis. Given its complexity and critical role in a number of important physiological processes, aberrant FGFR signaling has been found to be a driving force in tumor growth, promotion of angiogenesis, as well as conferring resistance to anti‑tumor therapies.
About HMPL‑453
HMPL‑453 is a novel, highly selective and potent small molecule inhibitor targeting FGFR 1, 2 and 3. In pre‑clinical studies, HMPL‑453 demonstrated superior potency and better kinase selectivity as compared to other drugs in the same class, as well as a favorable safety profile. Enrollment has been completed for the dose escalation of the Phase I study of HMPL-453 in China (clinicaltrials.gov identifier NCT03160833). Enrollment of a Phase II study is ongoing in patients with advanced malignant mesothelioma in China (clinicaltrials.gov identifier NCT04290325).