Benmelstobart

On 15 Apr 2023, the updated PFS & OS from the interim analysis (data cutoff Oct 14, 2021) of the study (NCT03910127) was reported at the AACR Congress, illustrating its potential clinical benefits and setting the stage for further exploration. Benmelstobart's R&D ProgressBenmelstobart is a monoclonal antibody drug that targets PDL1. It has a wide range of therapeutic areas, including neoplasms, infectious diseases, digestive system disorders, endocrinology and metabolic disease, urogenital diseases, respiratory diseases, immune system diseases, hemic and lymphatic diseases, mouth and tooth diseases, skin and musculoskeletal diseases, and otorhinolaryngologic diseases.  According to the Patsnap Synapse, Benmelstobart has reached the highest phase of development, NDA/BLA globally. And the clinical trial areas for Benmelstobart are primarily in the China. The key indication is Advanced Lung Non-Small Cell Carcinoma. Detailed Clinical Result of BenmelstobartThe randomized, parallel assignment, quadruple masking clinical trial (NCT03910127) was aimed to evaluate the efficacy and safety of TQB2450 alone/with Anlotinib in previously treated advanced non-small cell lung cancer.  In this study, adult patients with histologically or cytologically-confirmed stage IIIB or IV NSCLC who had wild-type EGFR/ALK and at least one line of prior systemic therapy or being intolerable of chemotherapy were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or anlotinib 10 or 12 mg. The primary end point was PFS and secondary endpoints included safety and OS.  The result showed that Between July. 2019 and March. 2021, 101 pts were enrolled. 33 patients were randomly assigned to TQB2450 plus placebo and 68 patients to TQB2450 plus anlotinib. As of 19 September 2022, The median follow-up was 26.3 months. The median PFS (7.3 months, 95% CI 5.3-11.0) for TQB2450 plus anlotinib was significantly longer than that for TQB2450 plus placebo group (2.8 months, 95% CI 1.4-4.7) (HR 0.39, 95% CI 0.23-0.64; P=0.0001). In patients with PD-L1 ≥ 1%, the mPFS was 17.9 months (95% CI 5.8-31.1) in TQB2450 plus anlotinib 12 mg, which was numerically higher than that in TQB2450 plus anlotinib 10 mg. The median OS of patients with PD-L1 ≥ 1% for TQB2450 plus anlotinib 12 mg was numerically higher than that in TQB2450 plus anlotinib 10 mg (32.2 months vs 21.8 months). Grade 3 or higher TRAEs occurred in 50.0% of the patients in TQB2450 plus anlotinb and in 12.1% of those in TQB2450 plus placebo. It can be concluded that in this updated analysis with longer follow-up, TQB2450 combined with anlotinib continues to demonstrate overall efficacy and manageable safety profiles in chemotherapy treated patients with advanced NSCLC without driver gene mutations. How to Easily View the Clinical Results Using Synapse Database?If you want to know the other clinical results of popular conferences, please lick on the “Clinical Results” on the homepage of Patsnap Synapse, which provides multi-dimensional screening and filtering of drugs, indications, targets, companies, result evaluation, release date, popular conferences, etc. to help you quickly locate the data you need.  Select the clinical meeting you are interested in, such as ESMO. In the results, you can quickly locate the data you want to view by indication, phase and drug name.  A single result clearly shows important information such as registration number, phase, indication, Sponsor/Collaborator, biomarker, Trial number, dosing regimen and more.  If you would like to view more information about this result, you can go to the result detail page by clicking on the title.  Above the headings, we provide the original source of the outcome data. The basic information is supplemented with more information beyond the list, such as company, study. design, etc.  In the important Outcome Measures section, we provide both list and flowchart forms, which are convenient for you to overview the comparison group information and core indicator data.  Finally, if you need to download these results, you can conveniently check the check boxes on the left side of the list, or directly click the "Export" button to download the data for personalized analysis and file sharing. Click on the image below to embark on a brand new journey of drug discovery!

Immunotherapy combining immune checkpoint inhibitors (ICIs) with anti-angiogenesis tyrosine kinase inhibitors (TKIs) has been shown to improve overall survival compared to anti-angiogenesis therapy alone in advanced solid tumors, but not in hepatocellular carcinoma. Dynamic duoRecently, a study has been published in The Lancet, which conducted a clinical trial comparing the efficacy and safety of the anti-PD-1 antibody camrelizumab combined with the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Between June 28, 2019 and March 24, 2021, 543 patients were randomly assigned to camrelizumab-rivoeranib (n=272) or sorafenib (n=271). In a preliminary analysis of progression-free survival with a median follow-up of 7.8 months (IQR 4.1-10.6), camrelizumab-rivoeranib significantly improved median progression-free survival compared to sorafenib (5.6 months [95% CI 5.5–6.3] vs 3.7 months [2.8–3.7]; hazard ratio [HR] 0.52 [95% CI 0.41–0.65]). In the overall survival analysis with a median follow-up of 14.5 months (IQR 9.1–18.7), median overall survival was significantly extended with camrelizumab-rivoeranib versus sorafenib. This study is registered as NCT03764293 and included in the Synapse database.  The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 in the sorafenib group), palmar-plantar erythrodysesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs 8 [3%]).  Treatment-related serious adverse events were reported in 66 (24%) patients in the camremizumab-rivoceranib group and 16 (6%) in the sorafenib group. There were two treatment-related deaths: one patient (multi-organ dysfunction syndrome) in the camrelizumab-rivoceranib group and one patient (respiratory and circulatory failure) in the sorafenib group.  ICIs and Anti-Angiogenic AgentsBased on the results of the SHARP, SHARP-Asia-Pacific, and REFLECT trials, sorafenib and lenvatinib (TKIs) have been established as the standard first-line treatment for unresectable hepatocellular carcinoma. However, the improvement in median overall survival compared to placebo is only marginal. In recent years, immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have emerged as new treatment options for advanced hepatocellular carcinoma. But only a small proportion of patients respond to ICI monotherapy, and no substantial survival increase over sorafenib has been observed with first-line treatment.  Immune checkpoint inhibitors mechanism of action against HCC tumor cells.To improve the immunosuppressive tumor microenvironment and enhance tumor response to immunotherapy, some phase 3 trials have evaluated ICIs plus anti-angiogenic agents as the first-line treatment for unresectable hepatocellular carcinoma. The global IMbrave150, COSMIC-312, LEAP-002, and Chinese ORIENT-32 trials have assessed this approach, and the results of combination therapy have been mixed. Only ICI plus anti-VEGF antibody has significantly improved overall survival, while multi-kinase TKIs have not. Oral TKIs are gaining attention due to their convenient administration, enhancing dosing flexibility via their shorter half-life. They also potentially eliminate the need for gastroscopy, which is required for bevacizumab therapy for hepatocellular carcinoma.  Furthermore, in the phase 3 HIMALAYA trial, dual immunotherapy with tremelimumab plus durvalumab demonstrated superior overall survival over sorafenib. However, the median overall survival of all systemic therapies in phase 3 trials of unresectable hepatocellular carcinoma is less than 2 years. Therefore, there remains a medical need for additional effective first-line regimens. Rivoeranib is a small molecule, highly selective VEGFR2-targeting TKI that exerts antitumor activity by inhibiting tumor cell proliferation and angiogenesis as well as by counteracting the immunosuppressive effects of the tumor microenvironment. Both camrelizumab and rivoeranib have shown efficacy and safety in advanced hepatocellular carcinoma and are approved in China as second-line monotherapies. In a phase 1 study in pretreated hepatocellular carcinoma and gastric or gastroesophageal junction cancer, camrelizumab plus rivoeranib demonstrated encouraging antitumor activity and acceptable tolerability. Subsequently, in a phase 2 trial in advanced liver cancer, camrelizumab combined with rivoeranib as second-line therapy showed improved clinical efficacy compared to historical data with camrelizumab or rivoeranib monotherapy; additionally, the objective response rate (ORR) with first-line combination treatment was 34.3% (95% CI 23.3–46.6), median progression-free survival was 5.7 months (95% CI 5.4–7.4), and 18-month overall survival was 58.1%. Significant improvementThis study is the first to report a phase 3 trial showing significant benefit in progression-free survival and overall survival with an anti-PD-1/PD-L1 antibody plus an oral small molecule TKI as first-line treatment for unresectable hepatocellular carcinoma. Camrelizumab-rivoeranib met the dual primary endpoints, demonstrating a 6.9-month improvement in median overall survival, a 1.9-month improvement in median progression-free survival (per BIRC RECIST 1.1) compared to sorafenib, with a 38% reduction in risk of death and 48% reduction in risk of progression or death. The survival benefits of combination therapy were supported by significantly higher response rates and more durable responses, as well as higher disease control rates compared to sorafenib. Preliminary analysis of progression-free survival and midterm analysis of overall survivalTumor objective responses evaluated using BIRC per RECIST 1.1 were in line with those evaluated using BIRC per modified RECIST and by investigators per RECIST 1.1. The improvement in ORR for camrelizumab-rivoeranib versus sorafenib (25% vs. 6% per RECIST 1.1) was consistent with that reported for atezolizumab-bevacizumab in IMbrave150 (30% vs. 11%), and better than atezolizumab-cabozantinib in COSMIC-312 (11% vs. 4%). Among all patients treated with camrelizumab-rivoeranib, 78% achieved disease control, and 35% of patients assessed for target lesions after the baseline had a tumor reduction of ≥30% with the combination, indicating a broad potential for clinical benefit. Camrelizumab plus rivoeranib demonstrated statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared to sorafenib, with manageable safety. The overall favorable benefit-risk profile supports camrelizumab plus rivoeranib as a new first-line treatment option for previously untreated patients with unresectable hepatocellular carcinoma. Reference S. Qin, S. L Chan et al., Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study, The Lancet, 2023, (23)00961-3.