Aveo, Eusa tout promise of tivozanib combo in kidney cancer
- Results from a Phase 1b/2 study testing Aveo Pharmaceuticals Inc. and Eusa Pharma's Fotivda together with Bristol-Myers Squibb & Co.'s Opdivo has given the companies confidence in further exploring combination therapies in renal cell carcinoma (RCC).
- Overall, the study enrolled 27 patients, with 14 patients evaluable for efficacy. Out of that smaller group, nine experienced a partial response and 5 saw their disease stabilize.
- Aveo characterized the combination as comparatively well-tolerated, reporting 44% of patients developed treatment-related Grade 3/4 adverse events. Combination therapy has attracted attention as a way of boosting the efficacy of immunotherapy, but safety is a key concern with layering treatments.
It has been a long slog towards the market for Fotivda (tivozanib), a tyrosine kinase inhibitor (TKI) now approved in Europe for advanced RCC.
In the U.S., however, Aveo is still working to secure an OK from the Food and Drug Administration. The regulator requested an additional study in 2012 before rejecting Aveo's application of approval in mid-2013.
Following a change of management, the requested study — a Phase 3 trial in advanced RCC known as TIVO-3 — got underway and topline data is expected in the second quarter of 2018.
The company expects data from TIVO-3, as well as results from the earlier TIVO-1 study, will support an application to the FDA for approval of tivozanib in first- and third-line RCC. The study which the companies reported preliminary results from last week, called TiNivo, explores tivozanib in combination with Opdivo (nivolumab).
Opdivo is currently approved to treat RCC following anti-angiogenic therapy.
As with other combinations involving immunotherapy, a principal concern with adding VEGF inhibitors to PD-1/L1 blockade is increased toxicity. Aveo and Eusa said the preliminary study results show the combination was generally well-tolerated, but more data will be needed to fully characterize the drug's profile.
"Combining VEGF TKIs and immune checkpoint inhibitors has been hampered by toxicity, potentially emerging with the use of other TKIs, while minimal off-target toxicities have been observed with tivozanib in this combination," said Bernard Escudier, the lead investigator of the study. "These results open the possibility for triple-combination therapy using tivozanib, nivolumab and ipilimumab, an immune system activator targeting CTLA-4."
Aveo CMO Michael Needle said the data support the further exploration of tivozanib combinations with immuno-oncology therapies.
Approval of Fotivda in Europe triggering a $4 million milestone payment for Aveo from partner Eusa Pharma. The drug also secured Monday a positive recommendation from the U.K.'s National Institute for Health and Care Excellence as a first line treatment for advanced renal cell carcinoma.
- Aveo Pharmaceuticals Inc. Press release
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