A pivotal Phase 3 clinical trial testing a combination of Cabometyx (cabozantinib) with Tecentriq (atezolizumab) versus standard care of Nevaxar (sorafenib) in previously untreated patients with advanced hepatocellular carcinoma (HCC) — the most common type of liver cancer — has begun.
The multi-center, randomized study (NCT03755791), sponsored by Exelixis and co-funded by Ipsen, is named COSMIC-312 and aims to include about 640 patients at up to 200 sites worldwide. Patient enrollment is ongoing at study sites in California and Nevada. (More information on study locations and contacts is available here.)
Participants will be assigned randomly to one of three treatment groups: Cabometyx (40 mg once a day) and Genentech’s Tecentriq (1,200 mg every three weeks), Bayer’s Nevaxar (400 mg twice per day), or stand-alone Cabometyx (60 mg once daily). Of note, while both Carbometyx and Nevaxar are delivered as oral tablets, Tecentriq is given intravenously.
The trial’s main goal is to determine if the Cabometyx-Tecentriq combination is better than Nexavar at extending the time patients live without signs of disease progression and extending overall survival. Therapeutic benefit with stand-alone Cabometyx therapy also will be evaluated.
Cabometyx targets receptors commonly expressed by cancer cells, such as MET, AXL, and VEGFR. They are known to be involved in several tumor processes, including new blood vessel formation, as well as tumor cell migration and invasiveness.
In turn, Tecentriq is a type of therapy called immune checkpoint inhibitor, which works by binding to the PD-L1 protein, found in both healthy and cancer cells. The binding of PD-L1 to PD-1 on immune T-cells helps cancer cells evade immune attack. Tecentriq is intended to block this interaction, boosting the immune response.
“Based on past evidence of potential synergistic effects with cabozantinib and immune checkpoint inhibitors, the combination offers promise for patients with advanced liver cancer who have not received prior treatment,” Gisela Schwab, MD, said in a press release. Schwab is Exelixis’ president of product development and medical affairs, and chief medical officer.
“We look forward to learning whether the combination of cabozantinib and atezolizumab may improve outcomes for previously untreated patients,” said R. Kate Kelley, MD, the study’s lead investigator.
Kelly, a professor of clinical medicine at the Division of Hematology/Oncology of University of California San Francisco further said that the more than 800,000 new cases of liver cancer worldwide each year and the poor prognosis for patients with advanced disease mean “there is an urgent need to identify new treatment options.”
Exelixis and Ipsen have an exclusive licensing agreement for the joint commercialization and development of Cabometyx indications outside of the U.S. and Japan. Ipsen will have access to COSMIC-312 results to support potential future regulatory submissions. In the U.S., Cabometyx is being developed and commercialized exclusively by Exelixis, while, in Japan, the company collaborates with Takeda for these purposes.
A decision on whether to approve Cabometyx in the U.S. for previously treated patients with advanced HCC is expected until Jan. 14, following the acceptance of a supplemental new drug application for the therapy by the U.S. Food and Drug Administration.
Cabometyx is approved in the U.S. for the treatment of advanced renal cell carcinoma (RCC). It also is approved in the European Union (EU), Norway, Iceland, Australia, Switzerland, Canada, South Korea, Canada, Brazil and Taiwan for adults with advanced RCC previously on a VEGF-targeted therapy; in the EU for previously untreated intermediate- or poor-risk advanced RCC; and in the EU, Norway, and Iceland for adults with HCC previously treated with Nevaxar.