NCT03499626

Phase 1b of ASLAN001 (Varlitinib) in Patients With Advanced/ Metastatic Hepatocellular Carcinoma (HCC)

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

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 21 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

* 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.

Conditions

• Advanced/ Metastatic Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	ASLAN001	Starting dose at 300mg BD Dose level +1: 400mg BD (which is the target dose for this study) Dose reduction of ASLAN001 in event of adverse events grade 2 and above: Dose level -1: 200mg BD Dose level -2: 100mg BD

Timeline

• Start date: 2017-05-05
• Primary completion: 2019-05-05
• Completion: 2021-05-05
• First posted: 2018-04-17
• Last updated: 2018-04-17

Locations

1 site across 1 country: Singapore