Phase 1 study of H3B-6527 in subjects with advanced HCC
Research type
Research Study
Full title
An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma
IRAS ID
272163
Contact name
Debashis Sarker
Contact email
Sponsor organisation
H3 Biomedicine Inc.
Eudract number
2016-001915-19
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 14 days
Research summary
Research Summary
Globally, liver cancer is the second most common cause of deaths due to cancer. Although mortality rates have decreased over the past several decades in many types of cancer, the mortality rates for liver cancers have doubled. The most common type of primary liver cancer is hepatocellular carcinoma (HCC). Most patients with liver cancer are diagnosed at an intermediate or advanced stage of disease, when cures are often not possible. For patients with advanced disease, treatment options are limited and prognosis is poor.
Sorafenib and Lenvatinib are currently considered standard of care first line therapy for advanced HCC in the UK. However, these drugs demonstrate only modest efficacy and are associated with significant toxicities. New treatments for advanced HCC are therefore urgently required.
Fibroblast growth factor receptor 4 (FGFR4) is found on the surface of liver cells. Over-activation of FGFR4 signalling can lead to the development of liver cancer. H3B-6527 inhibits FGFR4 and has been shown to prevent tumour formation in mice. This suggests that H3B-6527 could have a therapeutic benefit in patients with HCC.
This is a first-in-human, open-label Phase 1 study, sponsored by H3 Biomedicine Inc., and will be conducted in two parts: a Dose Escalation phase (Part 1) and a Dose Expansion phase (Part 2). The primary objectives of this study are to determine the maximum tolerated dose and/or recommended Phase 2 dose of H3B-6527 and to assess the safety and tolerability of H3B-6527 as a single agent in patients with advanced HCC. H3B-6527 will be administered daily by mouth in 21-day cycles.
The UK is only involved in the Part 2 of the trial. Approximately 30-128 patients are planned to be enrolled. Each subject on treatment is anticipated to be 4 months. However, subjects may continue study treatment, as long as they demonstrate clinical benefit.
Summary of Results
As of 06-Jan-2019, 37 pts have been treated with H3B-6527 at doses of 300 to 1400 mg QD (23 pts in escalation; 14 in expansion). In dose escalation, a total of 17 patients with HCC, Child-Pugh A received prior systemic therapy including 100% with prior TKI and 35% with prior IO. 12% had hepatitis B virus and 47% had hepatitis C virus. H3B-6527 plasma levels increased with dose from 300 to 1000 mg QD and plateaued. H3B-6527 was rapidly absorbed with a tmax of ~2-3 h and showed a terminal half-life of ~4-5 h, following administration of 1000 mg (fasted). No dose-limiting toxicities or ≥ Grade 3 treatment-related AEs (TRAE) have been observed in escalation. Most common TRAEs (≥ 10%) were diarrhea, nausea, and vomiting. Based on safety, PK, and PD, 1000 mg QD was the recommended phase 2 dose. Durable stable disease and partial responses (PR) have been observed on the once daily fasted schedule; 2 of 17 pts with HCC achieved PRs and an additional 7 with stable disease were on treatment for ≥ 5 months.
REC name
East of England - Essex Research Ethics Committee
REC reference
20/EE/0003
Date of REC Opinion
20 Feb 2020
REC opinion
Further Information Favourable Opinion