Advanced/ Metastatic Hepatocellular Carcinoma Clinical Trial
Official title:
Phase 1b Open Label Dose Assessment Study of ASLAN001 (Varlitinib) in Patients With Advanced/ Metastatic Hepatocellular Carcinoma (HCC) With an Expansion Cohort in HCC Patients Expressing HER3 Who Have Progressed on First Line Sorafenib or Lenvatinib
This is a single-arm, allocation open label study. Phase 1 is a dose-finding phase in
patients with advanced/ metastatic hepatocellular carcinoma (HCC) who have progressed on
first line Sorafenib or Lenvatinib.
The primary objective of this study will be to establish the maximal tolerable dose (MTD) of
ASLAN001 (Varlitinib) in the study population
The secondary objectives include:
1. To evaluate the efficacy of ASLAN001 (Varlitinib), as measured by duration of response
(DoR), progression free survival (PFS), overall survival (OS) and disease control rate
(DCR)
2. To assess the ORR, DoR, PFS, DCR and OS by tumor EGFR/HER2/HER3/HER4 status
3. To identify tumor and host biomarkers predictive of treatment response or toxicity to
ASLAN001.
- There are currently no effective and approved second line treatment options for
advanced/ metastatic HCC.
- ASLAN001 (Varlitinib) is a small molecule tyrosine kinase inhibitor against HER1 (EGFR),
HER2, and HER4.
- In vivo studies on HER2/3 expressing HCC PDX models suggest inhibition of pERB B2/3,
pERK1 and pERK 2 with treatment with ASLAN001 (Varlitinib). Dose dependent inhibition of
Cdc2 and pAKT in HCC PDX models treated with ASLAN001 (Varlitinib) also suggest robust
inhibition of the PI3K pathway.
- EGFR overexpression in HCC and matched non tumor tissues were detected in (32.5%) and
(28.6%), respectively. Moreover, missense and silent mutations were detected in (39.4%)
and (33.3%) of HCC tissues, respectively.
- Determine the maximum tolerable dose (MTD) of ASLAN001 (Varlitinib) in
advanced/metastatic HCC patients.
- After the recommended dose is determined, the Phase Ib portion of the study will
evaluate the efficacy of ASLAN001 (Varlitinib) in HCC patients who have progressed on
Sorafenib.
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