Byvasda (bevacizumab biosimilar)

P3, N=492, Completed, Innovent Biologics (Suzhou) Co. Ltd. | Recruiting --> Completed | Trial completion date: Apr 2024 --> Jun 2023

Systemic treatment with molecularly targeted drugs and immune checkpoint inhibitors, such as sorafenib, lenflutinib, donafenib, atezolizumab plus bevacizumab, sintilimab plus IBI305, regorafenib, pembrolizumab and anti-Cytotoxic T Lymphocyte antigen 4 (CTLA-4) was recommended by guidelines, but with limited effectiveness for HCC patients with PVTT. In recent years, the comprehensive treatment of HCC has advanced greatly. This review aims to provide an insight into the treatment modalities available for HCC patients with PVTT.

There is no study focusing on noninvasive predictors for the efficacy of sintilimab (anti-PD-1) plus IBI305 (a bevacizumab biosimilar) treatment in advanced hepatocellular carcinoma (HCC). The calibration curve and decision curve analysis (DCA) showed that the nomogram had a good consistency and clinical utility. This study has established and validated a nomogram by incorporating the quantitative parameters of pretreatment CEUS and baseline clinical characteristics to predict the anti-PD-1 plus anti-VEGF treatment efficacy in advanced HCC patients.

Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Compared with sorafenib, sintilimab plus IBI305 (HR: 0.57, 95% CI: 0.43-0.75), camrelizumab plus rivoceranib (HR: 0.62, 95% CI: 0.49-0.78), and atezolizumab plus bevacizumab (HR: 0.66, 95% CI: 0.52-0.83) ranked in the top three in terms of OS. PD-1/PD-L1 inhibitors combined with anti-vascular endothelial growth factor (anti-VEGF)-targeting drugs have shown better therapeutic effects in the systematic treatment of patients with advanced hepatocellular carcinoma, and the combination of targeted and immune therapy modes should be further developed.

On progression after immunotherapy-containing regimens and for patients with contraindications for immunotherapies, most guidelines maintain the established treatment hierarchy, recommending lenvatinib or sorafenib as the preferred options, followed by either regorafenib, cabozantinib, or ramucirumab. Thus far, the first-line immune-based regimen of tremelimumab plus durvulumab has been integrated only in the American Association for the Study of Liver Diseases guidance document and the latest National Comprehensive Cancer Network guidelines and is recommended for patients with a high risk of gastrointestinal bleeding. Overall, in the first-line setting, both atezolizumab plus bevacizumab and sintilimab plus IBI305 (a bevacizumab biosimilar) received the highest ESMO-MCBS score of 5, indicating a substantial magnitude of clinical benefit...However, the newly reported combination of camrelizumab plus rivoceranib was associated with a significantly higher risk of treatment-related adverse events compared with atezolizumab plus bevacizumab (relative risk, 1.59; 95% CI, 1.25-2.03; P < .001). This narrative review found that atezolizumab plus bevacizumab is regarded as the primary standard of care for advanced HCC in the first-line setting. These findings from integrating the recommendations from scientific societies' guidelines for managing advanced HCC along with new data from cross-trial comparisons may aid clinicians in decision-making and guide them through a rapidly evolving and complex treatment landscape.

This is the first prospective phase 3 trial to show the benefit of anti-PD-1 antibody plus chemotherapy in patients with EGFR-mutated NSCLC who progressed on treatment with tyrosine-kinase inhibitors. Compared with chemotherapy alone, sintilimab combined with pemetrexed and cisplatin showed significant and clinically meaningful improvement of progression-free survival with an optimal safety profile. Sintilimab plus IBI305 plus chemotherapy continued to show progression-free survival benefit compared with chemotherapy alone in this second interim analysis with an additional 8-month follow-up.

NMA indicated that Carbozantinib+atezolizumab (P-score: 90%), sintilimab+IBI305 (P-score: 89%), and atezolizumab+bevacizumab (P-score: 88%) yielded the best OS benefits. In the refractory setting, both immunotherapy (HR: 0.57, 95% CI, 0.35-0.93) and targeted therapy (pooled HR: 0.74, 95% CI: 0.65-0.83) were effective in improving OS; regorafenib (P-score: 81%) and pembrolizumab (P-score: 79%) were the most effective regimen...Atezolizumab + bevacizumab (P-score: 99%) was the superior first-line regimen, while regorafenib (P-score: 71%) was the preferred second-line regimen... The systematic review and NMA of 23 RCTs found that immunotherapies may be more effective in viral etiologies. However, the best regimen in non-viral etiology is less conclusive. Our results inform the clinical practice and design of future clinical trials.

Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74; 95% CI 0·52-1·06) and sintilimab plus IBI305 (HR 1·02; 95% CI 0·67-1·55) in reducing the risk of death. Efficacy was associated with a higher risk of grade 3 adverse events.

In this interim analysis, sintilimab plus IBI305 plus cisplatin and pemetrexed was generally efficacious and well tolerated in patients with EGFR-mutated NSCLC who progressed after receiving EGFR tyrosine-kinase inhibitor therapy.

P2, N=50, Recruiting, Tianjin Medical University Cancer Institute and Hospital

Sintilimab plus IBI305 was well tolerated and was effective therapy for advanced HCC. Both serum concentrations of CD137 and tumor infiltration of M1 macrophages may serve as potential predictive biomarkers.

The abstract for this presentation has not been submitted or is currently under embargo until August 18, 2021 at 16:00 MDT.

Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients.

P3, N=450, Completed, Innovent Biologics (Suzhou) Co. Ltd. | Active, not recruiting --> Completed

Registered on 3 November 2016. Https://clinicaltrials.gov/.