FDA to Review Tecentriq-Avastin Combo for Newly Diagnosed Advanced Liver Cancers

FDA to Review Tecentriq-Avastin Combo for Newly Diagnosed Advanced Liver Cancers

Genentech has submitted an application to the U.S. Food and Drug Administration to extend the use of Tecentriq (atezolizumab), in combination with Avastin (bevacizumab), for the treatment of people with newly diagnosed, inoperable hepatocellular carcinoma (HCC), the most common type of liver cancer.

The supplemental biologics license application (sBLA) is being reviewed under the FDA’s real-time oncology review pilot program. This pilot is meant to explore a more efficient review process, so patients can more quickly gain access to treatments found safe and effective.

The application from Genentech, a subsidiary of Roche, was based on results from the IMbrave150 Phase 3 trial (NCT03434379), which is still recruiting participants at some of its 144 clinical sites.

The global, open-label study is assessing whether first-line therapy with Tecentriq and Avastin prolongs survival outcomes compared with standard-of-care treatment with oral Nexavar (sorafenib) in people with inoperable HCC who have not received prior systemic therapy.

Participants in IMbrave150 — a total of 501 — will be randomly assigned to receive the Tecentriq-Avastin combo, administered by intravenous (into-the-vein) injections on the first day of each 21-day cycle, or twice-daily oral Nexavar. They will receive the treatment until unacceptable toxicity or a loss of clinical benefit as determined by the investigator.

Roche announced in November that IMbrave150 had met both its primary efficacy endpoints, with the Tecentriq combination reducing the risk of death by 42% and the risk of disease worsening or death by 41%, in comparison with Nexavar.

The secondary objective of overall response rate also was met, as more patients responded to the combination (27%) than to Nexavar (12%).

Earlier this month, the company presented data on quality of life, another secondary measure of IMbrave150, at the American Society of Clinical Oncology (ASCO) 2020 Gastrointestinal Cancers Symposium, held Jan. 23-25 in San Francisco.

The oral presentation, “Patient-reported outcomes (PROs) from the Phase III IMbrave150 trial of atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC),” showed that the Tecentriq-Avastin combination delayed declines in patient-reported overall quality of life, and in some subdomains of quality of life.

Participants in IMbrave150 were given two health-related, quality-of-life questionnaires — the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC  QLQ-HCC18 — at different points in time during the trial. The questionnaire was given before treatment, every three weeks while receiving the therapy, and every three months after treatment discontinuation. More than 92% of the questionnaires were completed.

The researchers assessed a specific measure called “time to deterioration.” This was defined as the time to a 10-point decrease in patient-reported overall quality of life, and in the subdomains of physical functioning — the ability to perform daily activities — and role functioning, or the participant’s capacity to fulfill responsibilities typical for a specific age and social setting.

The patient reports showed that the Tecentriq combination delayed deterioration in all three measures of quality of life compared with Nexavar. Those receiving Tecentriq plus Avastin took a median of 11.2 months to experience a 10-point deterioration in overall quality of life, compared with 3.6 months for those on Nexavar.

Similarly, a 10-point decline in role functioning was seen after a median of 4.9 months on Nexavar, but after a median of 13.1 months for those given the combination. Role functioning decline also was delayed from a median of 3.6 months to 9.1 months on the Tecentriq-Avastin combo.

“Because it reflects both the effects of disease and the side effects of treatment, sustained or improved quality of life is particularly important for patients,” Peter R. Galle, MD, PhD, of the University Medical Center in Mainz, Germany, and lead author of the quality of life study, said in a press release.

“Patients with liver cancer are typically more fragile and frail than others. Toxicity of the treatments can be much more serious for these patients, and their quality of life can decline quite quickly,” Galle said.

Patient-reported data from IMbrave150 also indicated that the time to deterioration in appetite loss, fatigue, pain, and diarrhea were all longer among those receiving the Tecentriq combo.

Tecentriq belongs to a form of immunotherapy known as checkpoint inhibitors. It targets a protein called PD-L1 and blocks it, which helps activate cancer-fighting immune cells.

Avastin is an antibody that binds VEGF-A, a protein required for the growth of new blood vessels in tumors. It works as a tumor-starving agent that interferes with the tumor blood supply, helping to prevent tumor growth and spread.

The Tecentriq-Avastin combination received the FDA’s breakthrough therapy designation for HCC in July 2018, based on data from an ongoing Phase 1b clinical trial (NCT02715531).