Roche Announces New Data from GO30140 Trial: T+A Combination Therapy Demonstrates Superior Efficacy Over Monotherapy in Advanced HCC

On August 30, Roche (China) announced the latest data from Arm A of the GO30140 clinical study on the treatment of patients with unresectable or advanced hepatocellular carcinoma (HCC) at the 2019 Asia-Pacific Primary Liver Cancer Expert Meeting.

Immunotherapy Combination for Liver Cancer Sparks Heated Discussion, Potentially Offering Hope for Improved Survival Benefits in Patients with Advanced-Stage Disease

GO30140 is an international, multicenter, open-label Phase Ib clinical trial evaluating the safety and clinical efficacy of the immunotherapy combination regimen of the PD-L1 inhibitor atezolizumab (trade name Tecentriq) plus the anti-angiogenic agent bevacizumab (trade name Avastin) (hereinafter referred to as the “T+A regimen”) in various solid tumors.

The GO30140 study Group A data released this time are to observe the efficacy and safety of the T+A regimen in first-line treatment for patients with unresectable liver cancer and advanced liver cancer.

Data showed that the primary endpoint, the objective response rate (ORR) assessed by the Independent Review Facility (IRF) per RECIST 1.1 criteria, was 36%. Secondary endpoints included an ORR of 39% assessed by the IRF per HCC mRECIST criteria, a median overall survival (OS) of 17.1 months (13.8–NE), and median progression-free survival (PFS) of 7.3 months as assessed by the IRF per both RECIST 1.1 and HCC mRECIST criteria. Although the median duration of response (DOR) had not been reached, the disease control rates (DCR) assessed by the IRF per RECIST 1.1 and mRECIST 1.1 criteria both reached 71% as of June 14, 2019, with 76% and 68% of patients, respectively, maintaining ongoing responses.

In addition, the objective response rate (ORR) assessed by the central review and investigator assessment reached 36% and 33%, respectively (both based on RECIST 1.1 criteria), whereas the ORR for previous monotherapy was above 10%. According to the Independent Review Facility (IRF) assessments based on RECIST 1.1 and HCC mRECIST, complete response (CR) was achieved in 12 and 16 patients, respectively, corresponding to CR rates of 12% and 15%.

In terms of safety, no new safety issues related to the combination therapy were identified beyond the known safety events associated with atezolizumab and bevacizumab monotherapies.

This was not the first unveiling of data on the T+A regimen for the treatment of unresectable, advanced hepatocellular carcinoma (HCC). In July 2018, based on the study results from GO30140 presented at the 2018 ASCO Annual Meeting, the U.S. FDA granted “Breakthrough Therapy” designation to the T+A regimen as first-line treatment for advanced, unresectable HCC. The study data were also updated at that year’s ESMO Congress.

In addition to the GO30140 study updated herein, Roche has completed enrollment in another study, IMbrave150 (NCT03434379). This is an open-label, multicenter, randomized Phase III clinical trial designed to evaluate the efficacy of atezolizumab plus bevacizumab versus sorafenib as first-line treatment for patients with locally advanced, unresectable, or metastatic hepatocellular carcinoma (HCC).

Sorafenib is an oral multi-target, multi-kinase inhibitor and currently serves as a first-line treatment regimen for hepatocellular carcinoma (HCC). It was approved by the U.S. Food and Drug Administration (FDA) in 2007 as a systemic therapy for patients with HCC and received marketing approval in China in 2008.

The launch of sorafenib once reversed the situation where advanced hepatocellular carcinoma (HCC) was untreatable. However, sorafenib is associated with significant adverse effects, and data submitted to the Center for Drug Evaluation (CDE) indicate that its response rate in East Asian populations is less than 5%. In March 2018, Japan approved lenvatinib for first-line treatment of liver cancer, making it the second targeted therapy approved for first-line use in HCC.

Due to the limited number of available therapeutic options, previous statistics from scholars at the National Cancer Center indicated that between 2012 and 2015, the five-year survival rate for liver cancer in China ranked second to last among the 17 cancers surveyed. Over a ten-year period, the five-year survival rate increased by only 2 percentage points, rising from 10.1% to 12.1%.

Globally, liver cancer is the third leading cause of cancer-related deaths, with approximately 780,000 new cases and 750,000 deaths annually. Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer, accounts for about 85%-90% of all primary liver cancer cases. In China, there are approximately 466,000 new cases of liver cancer per year, representing 55% of the global total, and 422,000 deaths annually, making it the second leading cause of cancer-related mortality after lung cancer.

Current treatment options for liver cancer include surgery, transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), local ablation, and systemic therapy (chemotherapy and targeted therapy). For patients with early-stage liver cancer, surgery is the preferred treatment option; however, due to the lack of obvious symptoms in the early stages, most patients have already reached locally advanced stages or developed distant metastases at the time of diagnosis, making only about 15% of patients suitable for surgical resection.

For patients who have lost the opportunity for surgery, there is an urgent need for more effective therapeutic agents. In recent years, with advances in research on immune checkpoint inhibitors, the industry has pinned its hopes on PD-1 and PD-L1 inhibitors to bring more solutions to the field of liver cancer and improve survival benefits for patients with advanced-stage disease.

In 2017 and 2018, the U.S. FDA approved Opdivo and Keytruda, respectively, for second-line treatment of sorafenib-refractory hepatocellular carcinoma (HCC). However, this year, the phase III KEYNOTE-240 study evaluating Keytruda versus best supportive care (BSC) as second-line therapy for advanced HCC failed to meet the prespecified statistical criteria for its two primary endpoints: overall survival (OS) and progression-free survival (PFS). Similarly, the phase III CheckMate 459 trial investigating Opdivo versus sorafenib as first-line treatment for advanced HCC did not achieve statistical significance for its primary endpoint of OS (these results exclude the standalone CheckMate-459 bridging study conducted in China).

Consequently, the focus of research in the field has shifted to novel combination therapies. In the T+A regimen, bevacizumab can promote T-cell infiltration into tumors by reversing VEGF-mediated immunosuppression, thereby enhancing the efficacy of atezolizumab. In addition to the T+A regimen, updated data on the efficacy and tolerable safety profile of lenvatinib combined with pembrolizumab were presented during this year’s American Association for Cancer Research (AACR) Annual Meeting, with related studies currently ongoing.

Source: Jiemian News Author: Jin Miao (Jemma)