LBA26Updated 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.Table: LBA26Efficacy (CCOD: Jul 26, 2018; N = 68)a4 patients were unevaluable.Investigator-Assessed Response (confirmed per RECIST v1.1)ORR, n/N (%)23/68 (34%) CR1/68 (1%) PR22/68 (32%)SD, n/N (%)30/68 (44%)DCR (CR + PR + SD), %78% 16-wk DCR (CR + PR + SD ≥ 16 wk)68% 24-wk DCR (CR + PR + SD ≥ 24 wk)50%PD, n/N (%)11/68 (16%)ORR by region, n/n (%)bRegion data from 1pt are missing. Asia (excluding Japan)12/37 (32%) Japan/US10/30 (33%)ORR by aetiology, n/n (%) HBV11/33 (33%) HCV10/22 (46%) Non-viral2/13 (15%)ORR by AFP, n/n (%)cBaseline AFP data from 5 pts are missing. <400 ng/ml12/38 (32%) ≥400 ng/ml11/25 (44%)ORR by EHS and/or MVI, n/n (%)dEHS and MVI baseline data from 2 pts are missing. +, censored observation; AFP, a-fetoprotein; CCOD, clinical cutoff date; EHS, extrahepatic spread; MVI, microvascular invasion; NE, not estimable; NR, not reached. Yes18/57 (32%) No4/9 (44%)Investigator-Assessed PFS per RECIST v1.1Median PFS (95% CI), mo14.9 (8.1, NE)Range, mo0.0+ to 23.9+Duration of Response per RECIST v1.1Median DOR, moNRRange, mo1.6+ to 22.0+a 4 patients were unevaluable.b Region data from 1 pt are missing.c Baseline AFP data from 5 pts are missing.d EHS and MVI baseline data from 2 pts are missing. +, censored observation; AFP, a-fetoprotein; CCOD, clinical cutoff date; EHS, extrahepatic spread; MVI, microvascular invasion; NE, not estimable; NR, not reached. Open table in a new tab Clinical trial identification: NCT02715531. Editorial acknowledgement: Medical writing for this abstract was provided by Steffen Biechele, PhD, of Health Interactions, Inc. Legal entity responsible for the study: F. Hoffmann-La Roche AG. Funding: F. Hoffmann-La Roche AG. Disclosure: M.J. Pishvaian: Consulting or advisory role: Caris Life Sciences, Perthera, Celgene, Sirtex Medical, AstraZeneca/MedImmune, RenovoRx; Travel, accommodations, expenses: Caris Life Sciences, Sirtex Medical, Perthera, AstraZeneca/MedImmune; Stock and other ownership interests: Perthera; Honoraria: Caris Life Sciences, Celgene, Sirtex Medical, Merrimack; Research funding to institution: Genentech, Celldex, Merck, GlaxoSmithKline, MedImmune, Pfizer, Gilead Sciences, Regeneron, Novartis, Karyopharm Therapeutics, Pharmacyclics, Bristol-Myers Squibb, Bayer, Curegenix, Calithera Biosciences, Tesaro, Bavarian Nordic, Halozyme, ARMO BioSciences, FibroGen, Celgene. M.S. Lee: Consulting or advisory role: Bayer; Research funding: EMD Serono, Genentech/Roche. S. Stein: Consulting or advisory role: Genentech/Roche. W. Verret, J. Spahn, B. Liu, K. Iizuka: Employee: Genentech, Inc. H. Shao: Employee: F. Hoffmann-La Roche Ltd. C-H. Hsu: Membership on an advisory board: BMS, Ono, MSD, Merck/Sorono, Novartis, Roche; Research funding: MSD. All other authors have declared no conflicts of interest.