Major Breakthrough in First-Line Liver Cancer Treatment: Roche’s Tecentriq plus Avastin Receives Positive CHMP Opinion for EU Approval

September 22, 2020 /BioValleyBIOON/ -- Roche recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the anti-PD-L1 therapy Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not previously received systemic therapy. The CHMP’s opinion will now be submitted to the European Commission (EC) for review, which typically renders a final decision within two months.

In terms of U.S. regulatory approval, the Tecentriq plus Avastin combination received FDA approval in May this year for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not previously received systemic therapy. This indication is based onFDAreviewed and approved under the Real-Time Oncology Review (RTOR) pilot program of Project Orbis. Most recently, the Tecentriq + Avastin combination was also approved in EuropeTumorThe European Society for Medical Oncology (ESMO) recommends it as a first-line therapy for unresectable hepatocellular carcinoma (HCC), and it has also been adopted by many clinical practice guidelines worldwide. In China, the application for this regimen was accepted by the National Medical Products Administration (NMPA) in January this year and was granted priority review status at the end of February.

It is worth noting that,Tecentriq + Avastin combination is the first and only cancer immunotherapy regimen approved for the treatment of unresectable or metastatic HCC.From IMbrave150Clinical TrialData show that, compared with the standard-of-care drug sorafenib, the combination therapy of Tecentriq plus Avastin significantly prolonged overall survival (OS) and progression-free survival (PFS).

Liver cancer is a leading cause of death worldwide, particularly in Asia, with hepatocellular carcinoma (HCC) being the most commonLiver CancerType. HCC primarily occurs in patients with cirrhosis caused by chronic hepatitis C (HCV) or alcohol consumption, and is often diagnosed at an advanced stage, leaving very limited treatment options.

IMbrave150 is in the most commonLiver CancerThe first Phase III cancer immunotherapy study to demonstrate improved OS and PFS with treatment.The combination of Tecentriq and Avastin is also the first treatment regimen to improve overall survival in patients with unresectable hepatocellular carcinoma who have not previously received systemic therapy, in over a decade.

Dr. Levi Garraway, Chief Medical Officer and Global Head of Product Development at Roche, stated: “The CHMP’s positive opinion recommending approval marks an important step toward bringing the Tecentriq + Avastin combination therapy to patients in Europe with advanced or unresectable hepatocellular carcinoma, representing a treatment for this fatal malignancy”Tumora significant milestone in this field.”

Professor Bruno Sangro, Director of the Liver Unit and Regional Coordinator for HPB Oncology at the University Clinic of Navarra in Pamplona, Spain, stated: “After more than a decade of therapeutic stagnation, the results of the IMbrave150 study are likely to change our approach to treating patients with hepatocellular carcinoma who are diagnosed with or have progressed to advanced stages. The study data show that, compared with currently selected tyrosine kinase inhibitors, the combination of Tecentriq and Avastin significantly prolongs patient survival and improves quality of life; moreover, in most patients, it can induce deep, durable, and sometimes completeTumorrelief.”

IMbrave150 (NCT03434379) is an open-label, multicenter, randomized Phase III study conducted in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma (HCC) who had not previously received systemic therapy. The study investigated the efficacy and safety of the combination regimen of Tecentriq and Avastin compared with the standard-of-care drug, the multikinase inhibitor sorafenib. In the study, patients were randomized in a 2:1 ratio to receive either Tecentriq plus Avastin (n=336) or sorafenib (n=165) until unacceptable toxicity occurred or clinical benefit was lost. The co-primary endpoints of the study were overall survival (OS) and progression-free survival (PFS), as determined by an independent review facility according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Results showed that, compared with the sorafenib group, the Tecentriq + Avastin combination therapy groupSignificantly prolonged overall survival (median OS: NE vs. 13.2 months), with a 42% reduction in the risk of death(HR=0.58, 95% CI: 0.42-0.79, p=0.0006), with an improved 12-month survival rate (67.2% vs 54.6%). Furthermore, compared to the sorafenib group, the Tecentriq + Avastin combination therapy groupSignificantly prolonged progression-free survival (median PFS: 6.8 months vs. 4.3 months), with a 41% reduction in the risk of disease progression or death（HR=0.59，95%CI:0.47-0.76，p＜0.0001）。

In this study, 38% of patients in the Tecentriq + Avastin combination therapy group experienced severeAdverse Reactions(Grade 3–4), the most common (>2%) were gastrointestinal bleeding, infection, and fever. These results were published this May in the New England Journal of Medicine (NEJM), a top-tier international medical journal.

Tecentriq is a PD-(L)1 tumor immunotherapy designed to target tumor cells andTumorBinds to a protein called PD-L1 expressed on infiltrating immune cells, blocking its interaction with the PD-1 and B7.1 receptors. By inhibiting PD-1, Tecentriq can activate T cells, and the drug has the potential to serve as a foundational combination therapy for cancer immunotherapy, targeted drugs, and various cancer chemotherapies.

Avastin is an angiogenesis inhibitor that targets and binds to vascular endothelial growth factor (VEGF). VEGF plays a critical role in angiogenesis and its maintenance throughout the tumor lifecycle. Avastin disrupts the tumor’s blood supply by directly binding to VEGF, thereby preventing its interaction with receptors on endothelial cells. The tumor’s blood supply is consideredTumorKey to in vivo growth and metastatic capacity.

Combining Tecentriq with Avastin is strongly supported by scientific evidence, as the Tecentriq plus Avastin regimen has the potential to enhance the immune system’s ability to combat tumors. In addition to its established anti-angiogenic effects, Avastin can also suppress VEGF-mediated immunosuppression, promote T-cell infiltration into tumors, and prime T cells againstTumorantigen response, further enhancing Tecentriq’s ability to restore the body’s anti-tumor immunity.

In December 2018, the U.S. FDA approved Tecentriq + Avastin + chemotherapy (carboplatin and paclitaxel) as first-line treatment for patients without EGFR or ALK genomic alterationsTumorAdult patients with metastatic non-squamous non-small cell lung cancer (NSq NSCLC) harboring alterations. This approval is based on data from Cohort B of the IMpower150 study: In intention-to-treat wild-type (ITT-WT) patients, Tecentriq plus Avastin plus chemotherapy significantly prolonged overall survival compared to Avastin plus chemotherapy (median OS: 19.2 months vs. 14.7 months; HR=0.78; p=0.016). (Bioon.com)

Original Source: Roche receives positive CHMP opinion for Tecentriq in combination with Avastin for the treatment of people with the most common form of liver cancer