Roche's Tecentriq plus Avastin Receives Approval in Japan and Priority Review in China for First-Line Treatment of Unresectable Hepatocellular Carcinoma

September 27, 2020 /BioonBIOON/ -- Chugai Pharmaceutical, a Japanese pharmaceutical company controlled by Roche, recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the anti-PD-L1 therapy Tecentriq (brand name: Tecentriq; generic name: atezolizumab) in combination with Avastin (brand name: Avastin; generic name: bevacizumab) for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not previously received systemic therapy. Recently, the Tecentriq plus Avastin combination also received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending approval, which is expected to be granted within the next two months.

In terms of U.S. regulatory affairs, the Tecentriq plus Avastin combination received FDA approval this May 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 plus Avastin combination was also approved in EuropeTumorThe European Society for Medical Oncology (ESMO) recommends it as a first-line treatment for unresectable hepatocellular carcinoma (HCC), and it has also been adopted by many clinical practice guidelines worldwide.In China, the application was accepted by the National Medical Products Administration (NMPA) in January this year and granted priority review status at the end of February.

It is worth mentioning that,Tecentriq + Avastin combination is the first and only cancer immunotherapy regimen approved for the treatment of unresectable or metastatic HCC.From IMbrave150Clinical TrialsData show that, compared with the standard-of-care drug sorafenib, combination therapy with 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 mainly occurs in patients with cirrhosis caused by chronic hepatitis (HCV) or alcohol consumption, and is usually diagnosed at an advanced stage, with very limited treatment options.

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

IMbrave150 (NCT03434379) was 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 evaluated the efficacy and safety of the combination regimen of Tecentriq plus Avastin compared with the standard-of-care drug, the multikinase inhibitor sorafenib. 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 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).

The results showed that, compared with the sorafenib group, the Tecentriq plus Avastin combination therapy group had a significantly prolonged overall survival (median OS: NE vs. 13.2 months), a 42% reduction in the risk of death (HR=0.58, 95% CI: 0.42-0.79, p=0.0006), and an improved 12-month survival rate (67.2% vs. 54.6%). Furthermore, compared with the sorafenib group, the Tecentriq plus Avastin combination therapy group demonstrated a significantly prolonged progression-free survival (median PFS: 6.8 months vs. 4.3 months) and 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 in May this year in the New England Journal of Medicine (NEJM), a top-tier international medical journal.

Tecentriq is a PD-(L)1 cancer 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 the PD-1 pathway, Tecentriq can activate T cells and has the potential to serve as a foundational combination therapy alongside cancer immunotherapies, targeted agents, and various chemotherapy regimens for multiple types of cancer.

Avastin is an angiogenesis inhibitor that targets and binds to vascular endothelial growth factor (VEGF). VEGF plays a crucial role in angiogenesis and maintenance during the tumor life cycle. Avastin disrupts the tumor's blood supply by directly binding to VEGF, thereby preventing its interaction with receptors on vascular 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.

December 2018, United StatesFDAApproval of 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 and chemotherapy significantly prolonged overall survival compared with Avastin plus chemotherapy (median OS: 19.2 months vs. 14.7 months; HR=0.78; p=0.016). (Bioon.com)

Original Source: Chugai Obtainsapproval for Additional Indication of Tecentriq and Avastin as the First Cancer Immunotherapy for Unresectable Hepatocellular Carcinoma