Top-line findings were presented today at the annual European Society for Medical Oncology (ESMO) Congress
This is the first positive pivotal trial to show survival benefits with a PD-1 inhibitor plus an anti-angiogenic TKI for uHCC
Sorafenib is a standard first-line treatment for uHCC
PARIS, Sept. 10, 2022 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc., a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, today announced top-line results from the Phase 3 study of its drug candidate rivoceranib combined with camrelizumab versus sorafenib as a first-line therapy for unresectable hepatocellular carcinoma (uHCC). Camrelizumab plus rivoceranib significantly prolonged overall survival (OS) and progression-free survival (PFS), and improved overall response rate (ORR) versus sorafenib, a standard first-line treatment for uHCC. The findings were presented today during the annual Congress of the European Society for Medical Oncology (ESMO) in Paris.
“Camrelizumab (C) plus rivoceranib (R) vs. sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): a randomized, phase 3 trial,” was shared as a proffered paper presentation at ESMO. A pre-recorded video of Elevar’s presentation is now available for viewing.
This global, randomized, open-label trial (NCT03764293) included 543 patients (ITT population), 17.3% of whom were non-Asian. The study began in June 2019, reaching its primary endpoint in April 2022. Top-line data included:
Median OS for camrelizumab+rivoceranib was 22.1 mos. [95% CI 19.1-27.2] vs. 15.2 mos. [13.0-18.5]; hazard ratio (HR) 0.62 [95% CI 0.49-0.80]; 1-sided p<0.0001,
Median PFS for camrelizumab+rivoceranib was 5.6 mos. [95% CI 5.5-6.3] vs. 3.7 mos. [2.8-3.7]; HR 0.52 [95% CI 0.41-0.65]); 1-sided p<0.0001, and
Confirmed ORR for camrelizumab+rivoceranib was 25.4% (95% CI 20.3-31.0), compared to 5.9% (3.4-9.4) for sorafenib.
“The efficacy results were generally consistent across all subgroups and with those reported in the overall ITT population, suggesting the combination of rivoceranib and camrelizumab confers a benefit in a global unresectable HCC population,” said Saeho Chong, chief executive officer of Elevar.
In China, more than two-thirds of HCC cases are associated with hepatitis B virus (HBV) infection, and approximately 10% of cases are associated with hepatitis C virus (HCV). In the U.S., approximately 10% of HCC cases are estimated to be associated with HBV and 60% are estimated to be due to HCV (deMartel, 2015).
“In our uHCC trial, there was an overall consistent trend of prolonged PFS for patients in the camrelizumab plus rivoceranib arm compared to those in the sorafenib arm, irrespective of geographical region (Asian vs. non-Asian) or etiology (HBV vs. HCV vs. non-viral),” said Jan M. Van Tornout, M.D., MSc., chief medical officer of Elevar. “Specifically, the combination of camrelizumab and rivoceranib demonstrated efficacy among those with HCV-based etiology, which comprises the majority of U.S. HCC cases1.”
The following data from the trial compares OS HR and PFS HR in Asian vs. non-Asian populations and in patients with different virus-based etiology:
OS HR in Asian 0.66 (95% CI 0.51, 0.86) vs. non-Asian 0.55 (0.29, 1.02),
OS HR in HBV 0.66 (0.5, 0.87) vs. HCV 0.45 (0.18, 1.16) vs. non-viral 0.71 (0.37, 1.36),
PFS HR in Asian 0.55 (95% CI 0.45, 0.70) vs. non-Asian 0.56 (0.30, 1.07), and
PFS HR in HBV 0.53 (0.41, 0.68) vs. HCV 0.56 (0.22, 1.45) vs. non-viral 0.65 (0.36, 1.20)
“HCC is the most common type of liver cancer, which despite advances in surgery, transplantation and approval of systemic therapies, still conveys a poor prognosis and survival rate,” said Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston. “The combination of camrelizumab and rivoceranib shows potential to address what is clearly an unmet medical need for HCC patients globally.”
Elevar also announced at the American Society of Clinical Oncology (ASCO) annual meeting in June 2022 that in its Phase 2 clinical trial (Study RM-202) of rivoceranib monotherapy in patients with progressive recurrent or metastatic adenoid cystic carcinoma (R/M ACC), rivoceranib demonstrated clinical effectiveness, as indicated by substantially reduced tumor progression during the six months after rivoceranib treatment compared to the tumor progression during the six months prior to rivoceranib treatment.
“Based on the positive results of the combination study, Elevar plans to work closely with the U.S. Food & Drug Administration for submission of a New Drug Application (NDA) for rivoceranib in combination with camrelizumab as a treatment option for HCC,” said Chong. “In addition, Elevar anticipates submission of an NDA to the U.S. Food & Drug Administration for rivoceranib as a treatment option for ACC by the end of 2022.”
1. Yoshizawa H. Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: Projection to other countries in the foreseeable future. Oncology. 2002;62(Suppl 1):8–17. [PubMed: 11868791]; El-Serag HB, Rudolph KL. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76. [PubMed: 17570226]
About Hepatocellular Carcinoma (HCC)
HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need.
Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer et al.) and treatment settings.
Camrelizumab, under the brand name AiRuiKa®, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021.
Rivoceranib is the first small-molecule tyrosine kinase inhibitor (TKI) approved in gastric cancer in China (November 2014). Rivoceranib is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is co-developed by Hengrui Pharma in China and by Elevar Therapeutics, Inc. globally (excluding China). It has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Clinical studies are ongoing in multiple solid tumor types including gastric cancer (as a monotherapy and in combination with paclitaxel), hepatocellular carcinoma (HCC) (in combination with camrelizumab), adenoid cystic carcinoma (as monotherapy) and colorectal cancer (in combination with Lonsurf®). Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in HCC (U.S.). Elevar holds the global rights (excluding China) and has partnered for the development and marketing of rivoceranib with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is currently approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Hengrui Pharma, under the brand name Aitan®.
About Elevar Therapeutics
Elevar Therapeutics, Inc. is a rapidly growing, fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. Elevar’s lead proprietary drug candidates include rivoceranib and paclitaxel micellar (Apealea®). Rivoceranib, under the name apatinib in China, was developed by Hengrui Pharma in China and approved in China as a single agent for treatment of gastric cancer in 2014 and second-line advanced HCC in 2020. It has been granted orphan drug designation in the U.S., Europe and South Korea and has been clinically tested in more than 1,000 patients worldwide in numerous cancer indications. Apealea® is a non-Cremophor EL based formulation of paclitaxel that received marketing authorization by the European Commission in November 2018, making it Europe’s first non-Cremophor EL formulation of paclitaxel approved for use in ovarian cancer. Elevar has offices in Utah, California, Ireland and South Korea. Additional information is available at ElevarTherapeutics.com.