Genentech Submits sBLA for Atezolizumab Plus Bevacizumab Combo to Treat Unresectable HCC

January 27, 2020

The company’s application is based on results from the phase III IMbrave150 study of the regimen for the treatment of patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.

A supplemental biologics license application (sBLA) has been submitted to the FDA for atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy, according to Genentech, the agent’s developer.

The application is being reviewed under the Real-Time Oncology Review pilot program and is based on results from the phase III IMbrave150 study. The results for the study were presented at the European Society for Medical Oncology (ESMO) Asia Congress in November 2019.

“Liver cancer is the most rapidly increasing cause of cancer-related death in the United States. In the IMbrave150 study, Tecentriq in combination with Avastin became the first treatment in more than a decade to improve overall survival compared with the current standard of care,” Levi Garraway, MD, PhD, chief medical officer and head of global Product Development for Genentech, said in a press release. “We are pleased that these results are being reviewed under the FDA Real-Time Oncology Review pilot program, and we are working closely with the agency to bring this potential new treatment option to people with unresectable hepatocellular carcinoma as quickly as possible.”

In the multicenter cohort of 501 people with unresectable HCC who had not received prior systemic therapy, participants were randomized 2:1 to receive the combination of atezolizumab and bevacizumab or sorafenib (Nexavar). Atezolizumab was administered intravenously (IV) to patients at 1200 mg on day 1 of each 21-day cycle, and bevacizumab was administered IV at 15 mg/kg on day 1 of each 21-day cycle. Participants receiving sorafenib were given the medicine orally at 400 mg twice per day, on days 1-21 of each 21-day cycle. Patients received either the combination or the control arm treatment until acceptable toxicity or loss of clinical benefit was determined by the investigator.

The combination therapy improved overall survival by 42% (hazard ratio [HR], 0.58; 95% CI, 0.42-0.79;P = 0.0006) and progression-free survival by 41% (HR, 0.59; 95% CI, 0.47-0.76;P < 0.0001), compared with sorafenib. Safety profiles for atezolizumab and bevacizumab were consistent with the known safety profiles of the individual medicines.

Patient reported outcomes from the trial, presented at the 2020 Gastrointestinal Cancers Symposium, held in San Francisco, California, from January 23-25, found that the overall response rate was 27% for the combination therapy and 12% for sorafenib. Additionally, time to deterioration, assessed by 2 validated patient-reported quality of life tools, was a median of 11.2 months for atezolizumab in combination with bevacizumab compared with 3.6 months for sorafenib. Declines in physical functioning were also slowed, with a median delay of 13.1 months observed with the combination treatment compared to 4.9 months with sorafenib.

The developer has a wide-ranging program for atezolizumab, in which the agent is being evaluated both alone and in combination with other medicines. The program includes multiple ongoing and planned phase III studies across several types of lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancer.

In July 2018, the FDA granted Breakthrough Therapy Designation for atezolizumab in combination with bevacizumab in HCC based on data from the ongoing Phase Ib trial.

According to the American Cancer Society, approximately 75% of liver cancers are HCC. The organization estimates that 42,810 new cases of liver cancer will be diagnosed in the US this year, and 30,160 people will die from the disease.

References:
1. Genentech Submits Supplemental Biologics License Application to the FDA for Tecentriq in Combination with Avastin for the Most Common Form of Liver Cancer [news release]. San Francisco, California. Published January 27, 2020. businesswire.com/news/home/20200126005034/en/. Accessed January 27, 2020.
2. New Drug Combinations Maintain Quality of Life for Patients with Colorectal and Liver Cancers [news release]. Alexandria, Virginia. Published January 21, 2020. asco.org/about-asco/press-center/news-releases/new-drug-combinations-maintain-quality-life-patients. Accessed January 27, 2020.
3. American Cancer Society. Cancer Facts & Figures 2020. American Cancer Society website. Published 2020. cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed January 27, 2020.