LAUSR

Abstract Background Tivozanib is a VEGFR-TKI with high specificity and lower incidence of class effect adverse events. We have previously reported encouraging preliminary results for objective response rates and tolerability for tivozanib and nivolumab at full dose of each drug. We report herein results for progression-free survival for this phase Ib/II combination study. Methods In the phase II portion of the study, tivozanib was administered orally at 1.5 mg, once daily for 21 days every 28-day cycle in combination with nivolumab 240 mg every 14 days intravenously to 22 patients. Included here are the 3 patients who received 1.5 mg of tivozanib in phase I for a total of 25 patients. Results 25 patients were treated with full dose tivozanib, 1.5 mg daily for 21 days. The median age was 62; 8 patients were IMDC favorable; 19 IMDC intermediate; 1 IMDC poor. 15 patients were ECOG 0 and 10 ECOG 1; and there were 19 males. 22 had clear cell histology. Median PFS is 18.9 months (95% CI 16.4; NR). PFS for previously untreated patients is 18.5 months and for previously treated patients the median has not been reached. ORR is 56% including 1 unconfirmed PR. There was 1 CR. DCR is 96%. All patients experienced at least one AE. 56% experienced a grade 3/4 AE related to treatment. The most common grade 3/4 adverse events related to treatment was hypertension seen in 44% of patients. Fatigue and palmar plantar dysesthesia were seen in 2 patients each. Conclusions The combination of tivozanib with nivolumab at full dose of both agents and leads to a high rate of prolonged disease control in both treatment naive and previously treated metastatic RCC with an overall median PFS of 18.9 mos. This promising combination compares well with other TKI-IO combinations and deserves further evaluation. Clinical trial identification NCT03136627. Legal entity responsible for the study AVEO Oncology. Funding AVEO Oncology. Disclosure P. Barthelemy: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Novartix; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Honoraria (self): Janssen; Advisory / Consultancy: Sanofi; Honoraria (self): Astellas; Advisory / Consultancy: BMS. B. Escudier: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: EUSA; Research grant / Funding (institution): Aveo. S. Negrier: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): EUSA; Honoraria (self): Novartis. A. Ravaud: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen. M.N. Needle: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Aveo Oncology. L. Albiges: Advisory / Consultancy, Institutional: Novartis; Advisory / Consultancy, Institutional: Pfizer; Advisory / Consultancy, Institutional: MSD; Advisory / Consultancy, Institutional: BMS; Advisory / Consultancy, Institutional: Ipsen; Advisory / Consultancy, Institutional: Roche; Advisory / Consultancy, Institutional: AstraZeneca.