A supplemental Biologics License Application has been submitted to the FDA for the combination of atezolizumab and bevacizumab or the treatment of patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy, according to a press release from Roche.
A supplemental Biologics License Application (sBLA) has been submitted to the FDA for the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy, according to a press release from Roche.1
The sBLA for atezolizumab/bevacizumab follows a Breakthrough Therapy Designation granted by the FDA in July of 2018, based on data from an ongoing phase Ib study.
TheIMbrave studyrandomized 501 patients with unresectable HCC and no prior systemic therapies in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib (Nexavar) alone. Results from the trial, which were presented at the European Society for Medical Oncology (ESMO) Asia Congress 2019, led to the sBLA for atezolizumab plus bevacizumab. The combination reduced the risk of death in patients with HCC by 42% compared with sorafenib monotherapy (HR, 0.58; 95% CI, 0.42-0.79; P<.0006). Progression-free survival (PFS) was also improved with atezolizumab and bevacizumab by 41% (HR, 0.59; 95% CI, 0.47-0.76;P<.0001). In the combination arm, the median overall survival (OS) was not reached versus 13.2 months in the sorafenib arm. The median PFS was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months in those who received sorafenib.
“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 OS compared with the current standard of care,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development.
Grade 3/4 adverse events (AEs) occurred in 57% of patients in the combination arm and 55%
of patients in the control arm. Five percent of patients and 6%, respectively, experienced grade 5 AEs.2
In the study, atezolizumab was administered intravenously (IV) at 1200 mg on day 1 of each 21-day cycle, and bevacizumab was given IV at 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered orally at 400 mg twice per day on days 1 through 21 of each 21-day cycle. Patients in both arms continued their treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
The coprimary end points of the study were OS and PFS by independent review facility, per RECIST v1.1. The secondary end points included objective response rate, time to progression, and duration of response by investigator assessment as measured by RECIST v1.1, as well as patient-reported outcomes, safety, and pharmacokinetics.
Patients were eligible to enroll in the IMbrave150 study if they had locally advanced or metastatic and/or unresectable HCC, at least one measurable untreated lesion, and an ECOG performance status of 0 or 1. Patients could not have received prior systemic therapy for HCC and were required to have adequate hematologic and end-organ function and be Child-Pugh class A. Individuals were excluded from the study due to previous malignancies or comorbidities that may have interfered with treatment during the study.
Atezolizumab plus bevacizumab in combination with carboplatin and paclitaxel has FDA approval for the treatment of metastatic nonsquamous nonsmall cell lung cancer (NSCLC). Atezolizumab, a monoclonal antibody inhibiting PD-L1, has multiple FDA approvals for the treatment of NSCLC, small cell lung cancer, PD-L1–positive metastatic triple-negative breast cancer, and certain types of urothelial cancer. Bevacizumab, a VEGF inhibitor, has FDA approval for the treatment of glioblastoma. Bevacizumab also has indications in combination with other drugs for the treatment of advanced and recurrent ovarian cancer, metastatic colorectal cancer, metastatic cervical cancer, and kidney cancer.