varlitinib (ASLAN001)

No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

P1/2, N=27, Completed, Yonsei University | Active, not recruiting --> Completed | N=62 --> 27

No abstract available

Oral cancer cells show proteome shift based on varlitinib treatment compared to corresponding controls. Our data suggest candidature of varlitinib as a potent therapeutic agent and BiP, PDIA1, HSP7C, VIME, and β-Actin as complementary/prognostic markers of OSCC.

The therapeutic responses differed across tumors' locations; the magnitude of the differences of responses across the tumors' locations were drug-dependent. Stratified analysis of the response by tumor location improved drug comparisons and is a powerful tool to understand TL heterogeneity.

Conclusions Varlitinib combined with paclitaxel revealed manageable toxicities and antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy. Updated outcomes for ongoing patients and biomarker analysis will be presented.

P1/2, N=62, Active, not recruiting, Yonsei University

The recommended phase II dose of varlitinib with paclitaxel is 300 mg twice daily intermittently dosed. This is active in HER2+ metastatic breast cancer. Subcutaneous trastuzumab can be added safely to varlitinib and paclitaxel. This combination is currently being evaluated as neoadjuvant therapy in HER2+ breast cancer (NCT02396108).

P2/3, N=52, Completed, Aslan Pharmaceuticals | Active, not recruiting --> Completed | N=400 --> 52

In patients with advanced biliary tract cancer, second-line treatment with varlitinib plus capecitabine was well tolerated but did not improve efficacy versus capecitabine alone. A PFS benefit was suggested in female patients and those with gallbladder cancer.

The upregulation of the ErbB family by EZH2 appears to contribute to infigratinib resistance. The combination of infigratinib and varlitinib showed a potent antitumour effect and did not result in additional toxicity, warranting further clinical investigation.

P1, N=60, Active, not recruiting, National Cancer Centre, Singapore | Recruiting --> Active, not recruiting | Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Jun 2020 --> Jun 2021

Background: EGFR and HER2 are over-expressed in gastric cancer, and activation of EGFR signaling in HER2-overexpressing gastric cancer can confer resistance to HER2-directed treatment like trastuzumab. The combination of varlitinib 300mg bid and weekly paclitaxel 80mg showed manageable safety profiles and determined as RP2D. Currently, multi-site phase 2 part is now underway.

A combination of varlitinib with PI3K inhibitor, BKM-120, was explored for efficacy in the KKU-100 cell line. Aspartate metabolite level was correlated with varlitinib response. Combination of varlitinib with targeted drug or cytotoxic drug was recommended.

Background: Patients with advanced or metastatic BTC who progress on first-line (1L) gemcitabine-based doublet chemotherapy have few 2L treatment options. V+C is well tolerated but did not improve ORR, PFS or OS vs. P+C in 2L advanced BTC. Exploratory analyses suggested that patients with GBC and female patients achieved comparatively higher median PFS with V+C vs.