Phase 1b/2 study of tivozanib in combination with durvalumab in subjects with advanced hepatocellular carcinoma (Deductive): Efficacy results in previously untreated patients.

Abstract

462 Background: The combination of a checkpoint inhibitor, atezolizumab, and angiogenesis inhibitor, bevacizumab, has improved the standard of care in advanced hepatocellular cancer with a median PFS of 6.8 months and 1-year overall survival of 67.2%. Tivozanib (a selective VEGFR 1,2 &3 TKI) has been combined with durvalumab in the phase I portion of the Deductive study (N=7) and the combination was well tolerated with the most common AEs being anorexia, cough, diarrhea, dysphonia, fatigue, hypertension and palmar-plantar erythrodysesthesia. (Ref: Iyer et al, JCO 39(3):294). Two of seven patients achieved a confirmed partial response. Here we report the preliminary efficacy data (PFS and OS) after 1 year of follow up of these patients. Methods: Major eligibility criteria included patients with age ≥18 yrs with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance > 40 ml/min. Major exclusion criteria included co-infection with HBV and HCV and significant organ dysfunction. The primary objective was to establish the RP2D and to determine the safety and tolerability for this combination in patients with advanced HCC. Secondary objectives included assessment of the ORR, PFS, and OS in this population. Results: Seven patients were enrolled in phase I part of the study. Two of seven patients achieved a confirmed partial response. Median PFS in this patient group was 7 months and 1-year survival was 80%. Kaplan-Meier plots of PFS and OS will be shown for patients with previously untreated advanced HCC. Conclusions: The combination of tivozanib and durvalumab in patients with untreated advanced HCC was considered tolerable and resulted in a median PFS of 7 months and 1-year overall survival of 80%. This is comparable to the outcomes seen with atezolizumab and bevacizumab. Enrollment is nearly complete with 19 of 20 patients in the front-line cohort enrolled; a second cohort of 20 patients who have progressed on prior bevacizumab and atezolizumab has been opened and is also enrolling. Data for the first line cohort will be presented at the meeting. Clinical trial information: NCT03970616.