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Aveo Oncology’s Fotivda combo fails in Phase 3 kidney cancer test

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Adding an immune checkpoint inhibitor did not improve the performance of Aveo Oncology’s Fotivda in a late-phase study in certain patients with renal cell carcinoma, nipping the company’s hopes for a combination approval.

The Phase 3 TiNivo-2 trial investigated Fotivda plus Bristol Myers Squibb’s Opdivo versus Fotivda monotherapy in 343 people with advanced metastatic RCC whose tumors had progressed following immune checkpoint inhibitor treatment.

The combination arm did not meet the progression-free survival (PFS) primary endpoint, according to a Thursday release. However, the Fotivda control arm achieved a “clinically meaningful outcome” in the same endpoint in second-line patients, the company said.

Immune checkpoint-based regimens are currently the standard of care in first-line advanced or metastatic RCC. The full results will be presented at an upcoming medical meeting, Aveo said.

The tyrosine kinase inhibitor won FDA approval back in 2021 for people with relapsed or refractory advanced RCC who have had two or more prior treatments, an approval that was a challenge for Aveo to secure.

A decade earlier, it shared data from a Phase 3 test that claimed tivozanib (the scientific name of Fotivda) could block all three VEGF receptors in kidney cancer, without disclosing to investors that the FDA had actually advised it to conduct another trial.

In 2013, an FDA panel voted against the drug’s risk-benefit profile, citing a 25% increase in the risk of death. That year’s setback triggered multiple shareholder lawsuits and an SEC investigation, with Aveo forced to cough up $22 million in settlements and losing its former partner Astellas in 2014.

The drugmaker then carried out another Phase 3 study comparing tivozanib with Bayer’s Nexavar in the third-line plus setting, which culminated in the 2021 US approval. In 2017, the drug was greenlit by the EMA for RCC patients who are VEGFR and mTOR pathway inhibitor-naive after one prior treatment with cytokine therapy.

South Korean chemical company LG Chem bought Aveo in 2022 for $566 million in an all-cash deal with an eye to growing a US base. At the time, Aveo said the buyout would give it the resources needed to explore Fotivda in other indications and ultimately expand its label.

Elsewhere, the drug is also in mid-stage development in combination with AstraZeneca’s Imfinzi in certain patients with hepatocellular carcinoma.


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