AZ begins liver cancer immunotherapy tie-up with AVEO

AZ’s Imfinzi (durvalumab) immunotherapy has suffered a series of setbacks but the Anglo-Swedish pharma is still trying to find ways to enhance the drug’s effects by combining it with other medicines.

In this case AZ is looking to combine Imfinzi, an anti PD-L1 class drug, with AVEO’s Fotivda (tivozanib), in first line hepatocellular carcinoma.

Fotivda is an oral, once-daily, potent and highly selective vascular endothelial growth factor tyrosine kinase inhibitor, and the two drugs will be initially tested in a phase 1/2 study.

AVEO will serve as the study sponsor, with study costs shared equally by both parties and clinical drug supplied by each respective company. The phase 1 portion of the study is expected to begin in 2019.

AVEO is also testing Fotivda in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) PD-1 cancer immunotherapy in renal cell carcinoma.

An oral, once daily, vascular endothelial growth factor tyrosine kinase inhibitor discovered by Kyowa Hakko Kirin, Fotivda inhibits all three VEGF receptors and is designed to minimise off-target toxicities and side effects.

The companies hope that this will have a synergistic effect with Imfinzi, which works by flipping a chemical switch, allowing the body’s own T-cells to recognise cancer cells and attack them.

Michael Bailey, president and CEO of AVEO, said: "We are thrilled to collaborate with AstraZeneca to explore another tivozanib-immunotherapy combination and look forward to understanding the potential of combining tivozanib with durvalumab in liver cancer.

"TKI-immunotherapy combinations have demonstrated important clinical potential across multiple tumour types, though toxicities associated with these combinations have limited their potential use. Our goal is to establish tivozanib as the TKI of choice for use with immunotherapies by demonstrating efficacy with reduced toxicity."

Fotivda is marketed in Europe and certain other countries by UK-based EUSA Pharma.

Although approved in a niche lung cancer use, and previously treated patients with bladder cancer, Imfinzi has failed in several other trials – most notably the lucrative first-line lung cancer indication where Merck’s Keytruda (pembrolizumab) is dominant.

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