Combination treatment with the VEGFR inhibitor tivozanib plus the anti-PD-L1 antibody durvalumab was found to be well-tolerated in patients with advanced hepatocellular carcinoma (HCC) who had not received prior therapy for their disease, according to the results of the phase 1b DEDUCTIVE trial presented at the Gastrointestinal Cancers Symposium.

The phase 1b portion of the study (ClinicalTrials.gov identifier: NCT03970616), which determined the recommended phase 2 dose (RP2D) to be 1 mg of oral tivozanib on days 1 through 21 plus 1500 mg of intravenous durvalumab on day 1 of each 28-day cycle, enrolled 7 patients with newly diagnosed, treatment-naïve, advanced HCC. The primary end point was establishment of the RP2D and assessment of the doublet therapy’s safety and tolerability in this patient population.

All patients were classified as Child-Pugh Class A. Patients were excluded if they had hepatitis B or C virus or significant organ dysfunction. At baseline, the median age was 75 years; 6 patients were male.


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Of the 7 patients enrolled, 2 achieved a partial response and 3 had stable disease. Progressive disease was reported in 2 patients.

One patient had mild elevation of LFTs, did not complete the 21-day course of tivozanib, and was subsequently replaced. Regarding toxicities, no patient experienced a grade 3 or higher adverse event (AE) in cycle 1. However, 1 patient developed a serious AE (grade 3 gastrointestinal hemorrhage).

The most common adverse drug reactions included cough, diarrhea, fatigue, hypertension, and palmar-plantar erythrodysesthesia. Each event was observed in 2 of 7 patients.

Existing data have validated the viability of combined VEGF and PD-L1 blockade. For example, bevacizumab plus atezolizumab was recently found to result in improved overall survival and progression-free survival vs sorafenib. The phase Ib findings add to the pool of available data on this approach.

The rationale for coadministering tivozanib and durvalumab derives from evidence demonstrating both therapies’ single-agent activity in the HCC arena. Of note, tivozanib selectively inhibits 3 different VEGFRs and therefore may provide an additional benefit.

A phase 2 trial to further evaluate this combination is now enrolling and aims to accrue an additional 30 patients.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by AVEO Oncology.

Reference

Iyer RV, Li D, Dayyani F, et al. DEDUCTIVE: a study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma; phase Ib results. Presented at: Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 294.

This article originally appeared on Cancer Therapy Advisor