945MO - AdvanTIG-206: Phase II randomized open-label study of ociperlimab (OCI) + tislelizumab (TIS) + BAT1706 (bevacizumab biosimilar) versus TIS + BAT1706 in patients (pts) with advanced hepatocellular carcinoma (HCC)

Background

Pts with advanced HCC have poor prognosis, with 5-year survival of 18%. Coinhibition of programmed death ligand-1 (PD-L1) and VEGF provides survival benefit in 1^st line (1L) HCC. In preclinical studies of HCC and clinical studies of other tumors, coinhibition of T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and PD-1 enhances antitumor activity of anti-PD-1. AdvanTIG-206 (NCT04948697) is investigating the efficacy/safety of adding OCI (anti-TIGIT) to TIS (anti-PD-1) + BAT1706 backbone as 1L therapy in advanced HCC pts.

Methods

Eligible adults had histologically confirmed HCC that is BCLC Stage B or C, not amenable to or progressed after loco-regional therapy, and with no prior systemic therapy. Pts were randomized 2:1 to OCI 900 mg + TIS 200 mg + BAT1706 15 mg/kg (O+T+B) or T+B every 3 weeks until loss of clinical benefit at investigator (INV) discretion. Primary endpoint was INV-assessed objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results

As of 27 Feb 2023, 94 pts (median age 58.5 years) were randomized to O+T+B (n=62) and T+B (n=32). INV-assessed ORR was 35.5% with O+T+B vs. 37.5% with T+B (Table). For O+T+B and T+B, respectively, Grade ≥3 treatment-related adverse events (TRAEs) were 50.0% and 25.8%, most common (≥5% incidence) TRAEs were hypertension (14.5% and 6.5%) and proteinuria (both 6.5%); TRAEs that led to any treatment discontinuation were 16.1% and 6.5%. Three (4.8%) treatment-related deaths occurred with O+T+B vs. none with T+B. Table: 945MO

Efficacy

Median follow-up was 9.2 months P-value is for descriptive purpose only. NE, not estimable ^aINV-confirmed per RECIST v1.1 ^bOnly includes pts with confirmed complete/partial response

Conclusions

In pts with advanced HCC, TIS + BAT1706 demonstrated promising ORR, while adding OCI to the doublet was not associated with improved anticancer activity. No new safety signals were identified in either arm. The OS data are premature and need further follow-up.

Clinical trial identification

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Smitha Reddy, PhD, and Nate Connors, PhD CMPP, of Envision Pharma Group, and was funded by BeiGene.

Legal entity responsible for the study

BeiGene.

Funding

BeiGene.

Disclosure

C. Dai: Financial Interests, Personal, Other, Grant: Education Department of Liaoning Province. V. Li, R. Abdrashitov, L. Wang: Financial Interests, Other, Employment: BeiGene. All other authors have declared no conflicts of interest.