Therapeutics: anticancer agent: varlitinib

Published: 1-Mar-2019

Human epidermal growth factors (HERs) are a group of receptors that are mutated or overexpressed in many tumour types; HER2 is the most familiar, as the target of the breast cancer antibody trastuzumab, but it is not alone

Varlitinib, being developed by Singapore-based Aslan Pharmaceuticals, is a potent, oral small molecule inhibitor of HER1, HER2 and HER4, all of which can lead to uncontrolled growth and excessive proliferation in tumour cells. It has potential as a treatment for various solid tumour types.

In a Phase Ib trial to investigate its potential in combination with cisplatin and either 5-fluorouracil or capecitabine, at the time of reporting 27 patients with various metastatic solid tumours had been enrolled.1

Varlitinib doses were escalated in a standard 3+3 design, with corresponding chemotherapy for six cycles; after this, they continued to receive varlitinib as a monotherapy. The most common treatment related adverse events were nausea, vomiting, decreased appetite, diarrhoea, anaemia and fatigue.

Of the 15 patients evaluable for response, three had a partial response, 10 achieved stable disease and the disease had progressed in the remaining two. Strong and durable responses were seen in cholangiocarcinoma; the liver tumour size of one patient was reduced by 87% by cycle two.

Another, who had no measurable lesions in either the liver or the biliary tract, achieved long-term disease control for 15 months, with good tolerability, on varlitinib as a monotherapy.

In a dose confirmation Phase Ib study, 37 patients with metastatic solid tumours were given varlitinib either with or without trastuzumab, in combination with weekly carboplatin or paclitaxel.2

The recommended dose of varlitinib was set at 300 mg with paclitaxel alone; the addition of trastuzumab was safe, with no dose limiting toxicities. Of the 20 patients who had HER2+ metastatic breast cancer, seven achieved partial response and three stable disease. Six had disease control with single agent varlitinib for a median 7 more months after chemotherapy.

Results of a Phase II study in first line gastric cancer have been announced via press release. In the placebo controlled, double blind trial in HER1/HER2 co-expressing advanced or metastatic gastric cancer patients, varlitinib plus mFOLFOX6 chemotherapy was compared with a placebo plus chemotherapy.

However, it did not meet the primary endpoint of significant reductions in tumour size after 12 weeks. Those given varlitinib had an average tumour shrinkage of 22.0% compared with 12.5% in the placebo group, a difference that does not reach statistical significance. There was a trend towards an improvement in progression free survival in the varlitinib group, and it was well tolerated.


  1. C-Y. Hsieh, et al., J. Clin. Oncol. 35(Suppl.), Abst. E15671 (2017).
  2. M. Lee, et al., J. Clin. Oncol. 36(Suppl.), Abst. 2588 (2018).

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