Byvasda (bevacizumab biosimilar) / Innovent Biologics, Etana - LARVOL DELTA

Integrating quality of life and overall survival to quantify benefit from frontline systemic therapy options in unresectable/advanced hepatocellular carcinoma: a network meta-analysis (EASL 2025) - " Ten studies, enrolling 7,268 patients treated with Sorafenib, Lenvatinib, Nivolumab, Tislelizumab, Durvalumab, Atezolizumab+Bevacizumab, Sintilimab+IBI305, Durvalumab+Tremelimumab, Nivolumab+Ipilimumab, Atezolizumab+Cabozantinib, Lenvatinib+Pembrolizumab, Camrelizumab+Apatinib were included... Atezolizumab plus Bevacizumab was associated with the highest magnitude in reducing the risk of deterioration of most HR-QoL domains compared to other systemic therapies. Integrated assessment of OS with HR-QoL assessed by MDC suggests atezolizumab plus bevacizumab to provide the best balance between QoL preservation and OS benefit compared to other systemic therapy options in unresectable/advanced HCC."

HEOR • Metastases • Retrospective data • Fatigue • Hepatocellular Cancer • Hepatology • Oncology • Pain • Solid Tumor

Updated network meta-analysis of first-line systemic therapies for advanced hepatocellular carcinoma: consistent role of TACE (EASL 2025) - " Transarterial chemoembolization (TACE) combined with lenvatinib provided the greatest improvement in OS compared to sorafenib, with a hazard ratio of 0.41 (95% confidence interval, 0.30–0.58), followed by sintilimab+IBI305 (0.57; 0.43–0.75), camrelizumab+rivoceranib (0.62; 0.48–0.80), atezolizumab+bevacizumab (0.66; 0.51– 0.85), lenvatinib+pembrolizumab (0.77; 0.62–0.97), and tremelimumab+durvalumab (0.78; 0.64–0.95). Our first-line analysis consistently scored TACE+lenvatinib best for survival outcomes, followed by various immunotherapy-based combinations in advanced HCC. This hierarchy was sustained in aggressive tumors or hepatitis B carriers."

Metastases • Retrospective data • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor

IFITM3: A predictive biomarker for therapeutic outcomes in advanced hepatocellular carcinoma (AACR 2025) - "Extracellular vesicles (EVs) are emerging as promising tools in cancer progression and therapy assessment. Sixty-five patients with China Liver Cancer (CNLC) stage III HCC treated with hepatic artery infusion chemotherapy (HAIC) plus sintilimab and a bevacizumab biosimilar (IBI305) were stratified based on RECIST criteria and surgical status for survival analysis and Kaplan-Meier (KM) curve construction. In summary, IFITM3 levels are closely linked to therapeutic outcomes in HCC patients. Non-invasive blood-based detection of IFITM3 holds promise for enhancing therapeutic stratification. Further research may refine prediction models and deepen understanding of IFITM3's role in poor therapeutic outcomes in cancer."

Biomarker • Metastases • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • DYNC1I2 • IFITM3

Updated Network Meta-Analysis of First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: Consistent Role of TACE (LCS 2025) - " Transarterial chemoembolization (TACE) combined with lenvatinib provided the greatest improvement in OS compared to sorafenib, with a hazard ratio of 0.41 (95% confidence interval, 0.30–0.58), followed by sintilimab+IBI305 (0.57; 0.43–0.75), camrelizumab+rivoceranib (0.62; 0.48–0.80), atezolizumab+bevacizumab (0.66; 0.51– 0.85), lenvatinib+pembrolizumab (0.77; 0.62–0.97), and tremelimumab+durvalumab (0.78; 0.64–0.95). Our first-line analysis consistently scored TACE+lenvatinib best for survival outcomes, followed by various immunotherapy-based combinations in advanced HCC. This hierarchy was sustained in aggressive tumors or hepatitis B carriers."

Metastases • Retrospective data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Sequencing of systemic therapy in unresectable hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis of randomized clinical trials. (PubMed, Crit Rev Oncol Hematol) - "We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study included high-quality multicenter Phase III RCTs, collated and summarized all treatments involved in advanced or unresectable HCC in first-line and second-line settings, and compared with T+A and regorafenib, respectively, and ranked based on efficacy and safety to support clinical decision making."

Clinical • Journal • Retrospective data • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Comparative restricted mean survival time (RMST) analysis of survival in advanced hepatocellular carcinoma (aHCC) from pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW. (ASCO-GI 2025) - "Angiogenesis inhibitor + immune checkpoint inhibitor combinations (Atezolizumab + Bevacizumab; Sintilimab + IBI305) provide the most favorable RMST outcomes in terms of OS and PFS. Restricted mean survival time (RMST) comparison of OS and PFS (months)."

Metastases • P3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

CAPOX Plus Sintilimab and Bevacizumab Biosimilar (IBI305) for Neoadjuvant Treatment of Locally Advanced Gastric Cancer (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: West China Hospital

Metastases • New P2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Sintilimab plus chemotherapy with or without bevacizumab biosimilar IBI305 in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapy: A China-based cost-effectiveness analysis. (PubMed, PLoS One) - "This study supports the cost-effectiveness of using sintilimab in combination with chemotherapy. Nevertheless, the cost-effectiveness of combining sintilimab with IBI305 and chemotherapy in this particular patient group may be lacking."

Cost effectiveness • HEOR • Journal • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Hepatic artery infusion chemotherapy (HAIC) plus sintilimab and bevacizumab biosimilar (IBI305) for initial unresectable hepatocellular carcinoma (HCC) in patients with Child-Pugh B liver function: A prospective study (ESMO 2024) - P2 | "Pts received modified FOLOFOX-HAIC (oxaliplatin 65 mg/m2, leucovorin 200 mg/m2, fluorouracil bolus 200 mg/m2, fluorouracil infusion 1200 mg/m2, every 3 weeks), with intravenous Sintilimab (200 mg) and IBI305 (7.5 mg/kg), also every 3 weeks. The modified regimen of FOLOFOX-HAIC with Sintilimab and IBI305, especially with tailored chemotherapy and targeted therapy doses, shows promising safety and efficacy for patients with unresectable HCC and Child-Pugh B liver function. This emphasizes the necessity of incorporating this subgroup into broader clinical trials."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

The Trend of the Treatment of Advanced Hepatocellular Carcinoma: Combination of Immunotherapy and Targeted Therapy. (PubMed, Curr Treat Options Oncol) - "Among the different combination therapy groups, atezolizumab plus bevacizumab and sintilimab plus IBI-305 seem to have unique advantages, while head-to-head comparisons are still needed. A comprehensive understanding of the developments, the ongoing clinical trials and the mechanisms of combination of immunotherapy and targeted therapy might lead to the development of new combination strategies and solving current challenges such as the molecular biomarkers, the clinical administration order of drugs and the second-line treatments after combination therapy."

IO biomarker • Journal • Metastases • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis. (PubMed, Cancer Med) - "As one of the promising immuno-combination therapies in the first-line systemic treatment of HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices."

Combination therapy • Cost effectiveness • HEOR • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

INOVA: Sintilimab Plus Bevacizumab in Recurrent/Persistent Ovarian Clear Cell Carcinoma (clinicaltrials.gov) - P2 | N=38 | Completed | Sponsor: Tongji Hospital | Recruiting ➔ Completed | Trial completion date: Apr 2024 ➔ Jul 2024 | Trial primary completion date: Apr 2024 ➔ Jul 2024

Trial completion • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer

Hepatic artery infusion chemotherapy (HAIC) plus sintilimab and bevacizumab biosimilar (IBI305) in initial unresectable hepatocellular carcinoma (HCC): A retrospective study. (ASCO 2024) - P2 | "Background: Combining sintilimab with IBI305 has shown significant survival benefits over sorafenib in first-line HCC treatment. Combining HAIC with Sintilimab and IBI305 as conversion therapy for unresectable HCC shows promising benefits with manageable safety."

Retrospective data • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor

Efficacy and safety of SBRT combined with sintilimab and IBI305 in patients with advanced HCC and previously failed immunotherapy: study protocol of a phase 2 clinical trial. (PubMed, BMJ Open) - "Dissemination of results will occur via a peer-reviewed publication and other relevant media. ChiCTR2200056068."

Clinical protocol • Journal • Metastases • P2 data • P2 data • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Predictive genomic biomarkers for atezolizumab plus bevacizumab combination immunotherapy response in liver cancer: Insights from the IMbrave150 trial (AACR 2024) - "Introduction: Combination immunotherapy regimens, exemplified by atezolizumab plus bevacizumab or sintilimab paired with a bevacizumab biosimilar (IBI305), have become the established standard of care for individuals with inoperable hepatocellular carcinoma (HCC)...Our aim is to evaluate whether previously defined immune signature scores (ISS) from the TCGA pan-cancer study can identify HCC patients likely to derive enhanced benefit from the combination immunotherapy. We applied ISS predictor to gene expression data from IMbrave150 clinical trial in which HCC patients were treated with atezolizumab plus bevacizumab or sorafenib and stratify the patients into responders and non-responders (cutoff of 0.5)... Our study suggests that ISS may serve as a promising predictive biomarker for enhanced therapeutic outcomes in patients undergoing combination immunotherapy for HCC. The identification of such markers is crucial for refining patient stratification and personalized..."

Biomarker • IO biomarker • Late-breaking abstract • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Comparability Strategy for an Unprecedented Post-Approval Production Cell Line Change of a Bevacizumab Biosimilar IBI305 (FOB-USA 2024) - No abstract available

Preclinical

Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial. (PubMed, Neoplasma) - "Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients."

Journal • P2 data • Cardiovascular • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Hypertension • Leukopenia • Oncology • Solid Tumor • Thrombocytopenia

New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis. (PubMed, J Clin Transl Hepatol) - "The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs...This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology."

Journal • Retrospective data • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor

Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis. (ASCO-GI 2024) - " A Markov model was built based on five global, multicenter, open-label, phase III randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A+B), sintilimab plus bevacizumab biosimilar (IBI305) (S+B), camrelizumab plus rivoceranib (C+R) and pembrolizumab plus lenvatinib (P+L). As one of the promising immuno-combination therapies in the first-line systemic treatment for unresectable HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices."

Clinical • Combination therapy • Cost effectiveness • HEOR • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Innovent Announces Inclusion in the China National Reimbursement Drug List of TYVYT's Seventh Indication and BYVASDA's Eighth Indication (PRNewswire) - "Innovent Biologics...announces that, the National Reimbursement Drug List (2023 Version) ('NRDL') has been updated to renew and include the seventh indication of PD-1 inhibitor TYVYT (sintilimab injection) in negotiation list, and include the eighth indication of BYVASDA (bevacizumab injection) in general list. The updated NRDL will officially take effect on January 1, 2024. In the updated NDRL, TYVYT expands its coverage to the seventh new indication for the treatment of patients with epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed after EGFR tyrosine kinase inhibitor (TKI) therapy. Meanwhile, BYVASDA as a combination medicine with TYVYT for the same indication, has its eighth indication included in the NRDL."

Reimbursement • Lung Non-Squamous Non-Small Cell Cancer

ORIENT-31: Sintilimab ± IBI305 Plus Chemotherapy (Pemetrexed + Cisplatin) for EGFRm + Locally Advanced or Metastasis Non-Squamous NSCLC Patients After EGFR-TKI Treatment Failure (clinicaltrials.gov) - P3 | N=492 | Completed | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Recruiting ➔ Completed | Trial completion date: Apr 2024 ➔ Jun 2023

Trial completion • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

COMPARISON OF FIRST-LINE SYSTEMIC THERAPIES FOR ADVANCED HEPATOCELLULAR CARCINOMA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (AASLD 2023) - "Compared to sorafenib, sintilimab plus a bevacizumab biosimilar (Sint-IBI305) showed the greatest OS benefit (HR=0.57, 95% CI=0.43–0.75, P score=0.944), followed by camrelizumab plus rivoceranib (Cam-Rivo; HR=0.62, 95% CI=0.49–0.79, P score=0.892) and atezolizumab plus bevacizumab (Atezo-Bev; HR=0.66, 95% CI=0.52–0.84, P score=0.834; Figure). Novel systemic therapies including Sint-IBI305 and Cam-Rivo demonstrated promising results compared to the current standard regimens (sorafenib, lenvatinib, and Atezo-Bev); however, further validation is warranted."

Metastases • Retrospective data • Review • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor

Network meta-analysis of first-line systemic therapies for advanced hepatocellular carcinoma: A comparison of objective response rates (ESMO 2023) - "The combination therapy of sintilimab + IBI305 had the highest ORR, with an RR of 13.6 (95% CrI: 3.69, 55.67) using fixed-effect and RR of 14.13 (95% CrI: 0.82, 120.1) using random-effect models. Conclusions The NMA revealed that the combination therapies had the highest ORR among the systemic therapies in the 1L setting. The SUCRA values confirmed the high probability of these treatments ranking higher in terms of ORR and can be used to support treatment decision-making in clinical practice."

Metastases • Retrospective data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Recent advances in treatment strategies for hepatocellular carcinoma with portal vein cancer thrombus. (PubMed, Eur Rev Med Pharmacol Sci) - "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."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • Thrombosis • Transplantation

Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305. (PubMed, Antib Ther) - "The comparability was further confirmed by comparable PK, pharmacodynamics, toxicological and immunogenicity profiles of nonclinical and clinical studies. The comparability strategy presented here might extend to cell line changes of other post-approval biological products, and particularly set a precedent in China for post-approval cell line change of commercialized biosimilars."

Journal • Preclinical