Abstract 1697
Background
Recently approved in the EU, tivozanib is a VEGFR-TKI with high specificity and lower incidence of class effect adverse events. We reported earlier that tivozanib can be combined with nivolumab at full dose of each drug. We report herein safety and efficacy data from a phase Ib/II combination of tivozanib and nivolumab.
Methods
In the phase Ib portion of the study, tivozanib was administered orally at 1.0 mg and 1.5 mg, once daily for 21 days every 28 day cycle using a standard 3 + 3 dose escalation design in combination with nivolumab 240 mg every 14 days intravenously. As there were no DLTs in phase I, in the phase II portion of the study tivozanib was administered orally at 1.5 mg in combination with nivolumab.
Results
28 patients have been enrolled, 6 in phase Ib and 22 in phase II. 25 were treated with full dose tivozanib, 1.5 mg daily for 21 days with nivolumab. The median age was 63; 8 patients were IMDC favorable; 19 IMDC intermediate; 1 IMDC poor. 18 patients were ECOG 0 and 9 ECOG 1; and there were 20 males. 24 had clear cell histology. All patients experienced at least one AE and 52% experienced a grade 3/4 AE. 44% experienced a grade 3/4 AE related to study drug. The most common grade 3/4 adverse events were hypertension, hand foot syndrome, and elevated lipase seen in 4, 2 and 2 patients respectively. The most common AEs (all grades) were hypertension, asthenia, arthralgia, dysphonia, mucocitis, diarrhea, and anorexia. 9 of the first 14 patients (64%) enrolled and treated with full dose tivozanib had a partial response. Final efficacy and safety data on all 28 patients will be available at the meeting.
Conclusions
The combination of tivozanib with nivolumab is safe and manageable at full dose of both drugs. The safety profile and the activity is favorable for a combination of a TKI with a checkpoint inhibitor as would be expected for a highly selective and well tolerated TKI.
Clinical trial identification
NCT03136627.
Legal entity responsible for the study
Aveo Oncology.
Funding
Aveo Oncology; Bristol Myers Squibb.
Editorial Acknowledgement
Disclosure
P. Barthelemy: Consulting relationship: BMS, Novartis, Pfizer, Roche, MSD; Honoraria: Janssen Cilag, Sanofi, Astellas. B. Escudier: Honorarium: Pfizer, Novartis, BMS, Roche, Ipsen, EUSA. A. Ravaud: Member of advisory boards in RCC: Pfizer, Novartis, BMS, Ipsen, Roche; Travel support for meetings or speeches: Pfizer, Novartis, BMS, Ipsen, Roche, AstraZeneca. S. Negrier: Honoraria: Pfizer, Ipsen, BMS, EUSA Pharma, Novartis; Research grant: Pfizer; Travel expenses: BMS, Pfizer, Ipsen. M.N. Needle: Full time employee, officer and shareholder: Aveo Oncology. L. Albiges: Consulting: Bristol-Myers Squibb, Pfizer, Novartis, Ipsen, Roche, Astellas Pharma, Merck, Amgen.
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