Abstract 945MO
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 1st 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
Best overall responsea, n (%) | O+T+B (n=62) | T+B (n=32) | |
Complete response | 0 | 0 | |
Partial response | 22 (35.5) | 12 (37.5) | |
Stable disease | 26 (41.9) | 11 (34.4) | |
Progressive disease | 10 (16.1) | 7 (21.9) | |
Not evaluable | 4 (6.5) | 2 (6.3) | |
ORR a , % (95% CI) | 35.5 (23.7, 48.7) | 37.5 (21.1, 56.3) | 2-sided P=0.8350 |
DOR b (months), median (95% CI) | 12.6 (7.0, NE) | 10.6 (4.2, NE) | |
PFS (months), median (95% CI) | 8.3 (5.5, 10.0) | 6.9 (4.1, NE) | Hazard ratio = 1.08 (0.59, 1.96) 1-sided P=0.4056 |
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.
Resources from the same session
94MO - Advanced extrahepatic cholangiocarcinoma: Post-hoc analysis of the ABC-01, -02 and -03 clinical trials
Presenter: Angela Lamarca
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
95MO - Tinengotinib in patients with advanced, fibroblast growth factor receptor (FGFR) inhibitor refractory/relapsed cholangiocarcinoma
Presenter: Meredith Pelster
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
Invited Discussant 945MO, 94MO and 95MO
Presenter: Lorenza Rimassa
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Slides
Webcast
LBA78 - Overall survival of perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy: An updated analysis of RESOLVE trial
Presenter: Xiaotian Zhang
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
1512MO - Perioperative camrelizumab (C) combined with rivoceranib (R) and chemotherapy (chemo) versus chemo for locally advanced resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The first interim analysis of a randomized, phase III trial (DRAGON IV)
Presenter: Chen Li
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
Invited Discussant LBA78 and 1512MO
Presenter: Hanneke van Laarhoven
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Slides
Webcast
LBA79 - GEMSTONE-303: Prespecified progression-free survival (PFS) and overall survival (OS) final analyses of a phase III study of sugemalimab plus chemotherapy vs placebo plus chemotherapy in treatment-naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma
Presenter: Xiaotian Zhang
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
LBA80 - Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus chemo as first-line (1L) treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Final analysis results of the RATIONALE-305 study
Presenter: Rui-Hua Xu
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
1513MO - A phase II study of nivolumab plus low dose ipilimumab as first -line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209-7W7)
Presenter: Kei Muro
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Abstract
Slides
Webcast
Invited Discussant LBA79, LBA80 and 1513MO
Presenter: Tania Fleitas
Session: Mini oral session 1 - Gastrointestinal tumours, upper digestive
Resources:
Slides
Webcast