2728 - Updated safety and clinical activity results from a Phase Ib study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC)

Background

Agents targeting angiogenesis or PD-L1/PD-1 signalling represent 2 types of approved treatments (tx) for HCC. In addition to its anti-angiogenic activity, bevacizumab (bev; anti-VEGF) has immunomodulatory effects that alter the tumour microenvironment, which may augment atezolizumab (atezo; anti–PD-L1)-mediated anti-tumour immune responses. This scientific rationale, including preclinical and clinical data, supports the hypothesis that the combination of atezo + bev may be effective in advanced HCC.

Methods

In a Phase Ib study cohort, patients (pts) with unresectable or metastatic HCC received atezo 1200 mg + bev 15 mg/kg IV q3w as first-line (1L) tx until loss of clinical benefit or unacceptable toxicity. The primary objectives were safety and efficacy based on investigator-assessed ORR per RECIST v1.1. Secondary endpoints included PFS and DOR per RECIST v1.1.

Results

As of Mar 23, 2018, 68 pts were safety evaluable. Any grade (Gr) tx-related AEs occurred in 49 pts (72%). Gr 3-4 tx-related AEs were seen in 17 pts (25%), most commonly hypertension (n=8 [12%]). 5 pts (7%) experienced Gr 3 tx-related serious AEs. No tx-related Gr 5 AEs occurred. Immune-related AEs requiring systemic corticosteroid tx occurred in 4 pts (6%). As of Jul 26, 2018, 68 pts were efficacy evaluable (follow-up ≥18 wk). The ORR was 34%. Responses were observed in all clinically relevant subgroups, including pts with AFP ≥400 ng/ml, EHS and/or MVI (Table). 19 of 23 confirmed responses were ongoing (≥6 mo in 11 pts). The 6-mo PFS rate was 71%. Median DOR and median OS have not yet been reached (DOR range, 1.6+ to 22.0+). Updated data (including IRF-assessed ORR and PFS per RECIST v1.1 and HCC mRECIST) will be presented.

Conclusions

With a tolerable safety profile, encouraging response rates and durable responses, atezo + bev may be a promising 1L tx option for pts with advanced HCC. The Phase III IMbrave150 trial (NCT03434379) is currently recruiting.

Clinical trial identification

NCT02715531

Editorial Acknowledgement

Medical writing for this abstract was provided by Steffen Biechele, PhD, of Health Interactions, Inc.