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

Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "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."

IO biomarker • Journal • P3 data • P3 data: top line • Gastrointestinal Disorder • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated non-squamous non-small cell lung cancer (EGFRm nsqNSCLC) who progressed on EGFR tyrosine-kinase inhibitors (TKIs) therapy: Second interim analysis of phase III ORIENT-31 study (ESMO 2022) - P3 | "Sin/pb1 (200 mg), IBI305/pb2 (15 mg/kg), pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) were administered IV Q3W for 4 cycles, followed by maintenance treatment of sin/pb1, IBI305/pb2 and pemetrexed. Grade ≥3 treatment-emergent adverse events occurred in 59.5%, 46.2%, and 56.9% pts respectively. Conclusions Sin combined with or without IBI305 and chemo significantly improved PFS in pts with advanced EGFRm nsqNSCLC who progressed on EGFR-TKI therapy, vs chemo alone."

Clinical • IO biomarker • Late-breaking abstract • P3 data • P3 data: top line • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial. (PubMed, Lancet Respir Med) - P3 | "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."

IO biomarker • Journal • P3 data • P3 data: top line • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

CapeOX (capecitabine and oxaliplatin) combined with sintilimab and bevacizumab biosimilar (IBI305) for first-line treatment of advanced gastric or oesophagogastric junction adenocarcinoma: study protocol for a single-arm, phase Ib/II trial. (PubMed, BMJ Open) - P1/2 | "The final results will be published in a peer-reviewed journal upon completion of the study. NCT05640609."

Clinical protocol • Journal • P1/2 data • Anal Carcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Stereotactic body radiotherapy with sintilimab and bevacizumab biosimilar in anti-PD-1 refractory hepatocellular carcinoma: the ReUNION-1 phase 2 trial (Nature, Nat Commun) - "Twenty-one patients with progressive HCC after ICI therapy receive SBRT followed by sintilimab 200 mg and bevacizumab biosimilar 15 mg/kg every 3 weeks. The primary outcome, objective response rate in non-irradiated lesions is 33.3%, with a disease control rate of 66.7%. Median progression-free survival is 6.2 months, and estimated median overall survival is 24.4 months. SBRT achieves 100% local control, with 33.3% experiencing grade 3 or higher adverse events."

P2 data • Hepatocellular Cancer

Stereotactic body radiotherapy with sintilimab and bevacizumab biosimilar in anti-PD-1 refractory hepatocellular carcinoma: the ReUNION-1 phase 2 trial (Nature, Nat Commun) - "Twenty-one patients with progressive HCC after ICI therapy receive SBRT followed by sintilimab 200 mg and bevacizumab biosimilar 15 mg/kg every 3 weeks. The primary outcome, objective response rate in non-irradiated lesions is 33.3%, with a disease control rate of 66.7%. Median progression-free survival is 6.2 months, and estimated median overall survival is 24.4 months. SBRT achieves 100% local control, with 33.3% experiencing grade 3 or higher adverse events."

P2 data • Hepatocellular Cancer

Crossover-adjusted overall survival (OS) benefit with sintilimab in EGFR-TKI-resistant NSCLC: Post-hoc analysis of ORIENT-31 (ESMO Asia 2025) - P3 | "Background: In Orient-31 (NCT03802240), baseline characteristics for sintilimab+IBI305+chemo (Arm A) and chemo-alone (Arm C) groups in EGFR-TKI-resistant NSCLC were reported. This crossover-adjusted analysis demonstrates a significant overall survival benefit for sintilimab-based therapy in EGFR-TKI-resistant NSCLC. Propensity score matching confirmed robust OS improvement (23.3 vs 15.0 months; HR 0.62, 95% CI 0.41-0.96; p=0.030), indicating conventional ITT analysis underestimated treatment efficacy due to crossover contamination."

Clinical • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Sintilimab plus a bevacizumab biosimilar (IBI305) in advanced HCC with Child-Pugh A/B liver function: a real-world multicenter retrospective study. (PubMed, Front Oncol) - "Sin/Bev demonstrated encouraging short-term anti-tumor activity in HCC of CP-A and CP-B, while survival outcomes were affected by differences in hepatic function. Although the regimen was generally well tolerated, patients with impaired liver reserve require vigilant monitoring and comprehensive supportive strategies to maximize therapeutic outcomes."

Journal • Real-world evidence • Retrospective data • Hematological Disorders • Hepatocellular Cancer • Liver Failure • Oncology • Solid Tumor • Thrombocytopenia

Sintilimab plus a Bevacizumab biosimilar (IBI305) in Advanced HCC with Child-Pugh A/B liver function: A Real-World Multicenter Retrospective Study (Frontiers) - "The objective response rates (ORR) of patients with CP-A and CP-B treated with 13 Sin/Bev were 50.7% and 57.7%, respectively, and both could achieve good anti-tumor 14 efficacy. CP-B had inferior survival: median OS (15 vs 22 months, p=0.044), PFS (8 vs 14 15 months, p=0.014), and TTD (7 vs 15 months, p<0.001). The CP-B cohort demonstrated 16 comparable incidence rates of grade 3-4 AEs to the CP-A group (34.6% vs 34.2%). 17 Hemorrhagic events and thrombocytopenia emerged as predominant grade 3-4 AEs in CP-B 18 patients (15.4% for both)."

Real-world • Hepatocellular Cancer

Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy as first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma (SBAGA): A single-arm, phase Ib/II study (ESMO 2025) - P1/2 | "The most frequently reported TRAEs were fatigue, nausea, and neutropenia, with 37 patients (66%) experiencing grade 3 AEs or higher, including neutropenia (14%) and fatigue (13%). Conclusions In conclusion, combining chemotherapy with sintilimab and IBI305 demonstrated higher ORR, longer PFS, and tolerable safety profile, making the phase III trial results highly anticipated."

Clinical • IO biomarker • Metastases • P1/2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

Economic evaluation of three domestic bevacizumab biosimilars and the original bevacizumab for treating nonsquamous non-small cell lung cancer in china: a cost-effectiveness analysis. (PubMed, Cost Eff Resour Alloc) - "Domestic bevacizumab biosimilars are cost-effective alternatives to first-line treatment for nonsquamous NSCLC in China. IBI305 exhibited the most significant cost-effective advantage among the domestic biosimilars."

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

A Study of IBI363 Combination Therapy in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

New P2 trial • Platinum resistant • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Updated Network Meta-Analysis of First-Line Systemic Treatments for Advanced HCC: Consistent Role of TACE. (PubMed, Liver Cancer) - "Transarterial chemoembolization (TACE) combined with lenvatinib provided the greatest improvement in OS over 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). For advanced HCC, our first-line analysis consistently scored TACE + lenvatinib the best for survival outcomes, followed by various immunotherapy-based combinations. However, the superior efficacy of TACE + lenvatinib should be interpreted with consideration of its derivation from a region with high hepatitis B virus prevalence."

Journal • Retrospective data • Review • Hepatitis B • Hepatocellular Cancer • Infectious Disease • Liver Cancer • Oncology • Solid Tumor

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