ESMO World GI 2017: Phase I Data on Anti–PD-1 Antibody BGB-A317 in Hepatocellular Carcinoma

Key Points

  • 27 patients were evaluable for response. Twelve of the evaluable patients remained on treatment and the majority (7) of these had only one tumor assessment at the time of the data cutoff. Confirmed and unconfirmed partial responses were observed in three patients, all with HBV-positive hepatocellular carcinoma.
  • Nine patients achieved stable disease, some of whom also had significant reductions in alpha-fetoprotein levels.
  • Adverse events assessed by the investigator to be related to treatment occurred in 21 patients (53%). Of those, rash, pruritus, increased aspartate aminotransferase, fatigue, hypothyroidism, and decreased appetite were reported in more than one patient.

Preliminary results from patients with advanced hepatocellular carcinoma enrolled in a phase I study of the investigational anti–programmed cell death protein 1 (PD-1) antibody BGB-A317 in advanced solid tumors were presented by Yen et al at the ESMO 19th World Congress on Gastrointestinal Cancer in Barcelona, Spain (Abstract P-140). The preliminary phase I data suggest that BGB-A317 was generally well-tolerated and exhibited preliminary evidence of antitumor activity in patients with hepatocellular carcinoma.

“Current treatment options for patients with liver cancer remain unsatisfactory. We are encouraged that in this trial, BGB-A317 demonstrated preliminary antitumor activity in patients with hepatitis B virus–positive hepatocellular carcinoma, a subtype typically associated with poor prognosis,” commented Chia-Jui Yen, MD, Associate Professor at the National Cheng Kung University Hospital, Tainan, Taiwan, and the lead author of the abstract.

Study Findings

The multicenter, open-label phase Ia/b trial of BGB-A317 as monotherapy in advanced solid tumors is being conducted in Australia, New Zealand, the United States, Taiwan, and South Korea, and consists of a phase Ia component (dose escalation, schedule expansion, and fixed-dose expansion) and a phase Ib component of indication expansion in disease-specific cohorts, which includes an hepatocellular carcinoma cohort.

Data presented at ESMO World GI were from 40 patients with advanced hepatocellular carcinoma who were treated with BGB-A317 at a dose of 5 mg/kg every 3 weeks. The majority of the enrolled patients (34 of 40 patients) had a hepatitis B virus (HBV) infection. At the time of the data cutoff on April 28, 2017, median treatment duration was 64 days (range of 1 to 471 days).

At the time of the data cutoff, the efficacy evaluation was early, and 27 patients were evaluable for response. Twelve of the evaluable patients remained on treatment and the majority (seven) of these had only one tumor assessment at the time of the data cutoff. Confirmed and unconfirmed partial responses (PRs) were observed in three patients, all with HBV-positive hepatocellular carcinoma. One PR was confirmed before the cutoff date, one was confirmed 1 day following the cutoff date, and one was unconfirmed and the patient remained on therapy. Nine patients achieved stable disease, some of whom also had significant reductions in alpha-fetoprotein levels.

Adverse events assessed by the investigator to be related to treatment occurred in 21 patients (53%). Of those, rash (20%), pruritus (13%), increased aspartate aminotransferase (8%), fatigue (5%), hypothyroidism (5%), and decreased appetite (5%) were reported in more than one patient. All of the treatment-related adverse events were grades 1 or 2, with the exception of one grade 5 event of acute hepatitis assessed by the investigator to be related to BGB-A317. This patient had widely metastatic disease and died 5 weeks after receiving his first and only dose of BGB-A317 and subsequently developing evidence of disease progression.

About BGB-A317

BGB-A317 is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1. BGB-A317 has high affinity and specificity for PD-1, and researchers believe it may be differentiated from the currently approved PD-1 antibodies, as the ability to bind to Fc gamma receptors has been specifically engineered out. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement