Camrelizumab

Bristol Myers Squibb's Opdivo and Yervoy helped 38% of patients with newly diagnosed liver cancer live past three years in a phase 3 trial, setting a new record. Following fellow immunotherapy regimens by Roche and AstraZeneca, Bristol Myers Squibb’s Opdivo and Yervoy want to carve out a piece of the first-line liver cancer market, too. The BMS immunotherapy duo pared down the risk of death by 21% compared with either Merck and Eisai’s Lenvima or Bayer’s Nexavar in patients with previously untreated advanced hepatocellular carcinoma, according to data from the phase 3 CheckMate-9DW trial. Specifically, patients who received Opdivo and Yervoy lived 3.1 months longer than those who got either one of the two tyrosine kinase inhibitors at the median, reaching 23.7 months. The results were shared Tuesday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. What was unclear, though, is whether Opdivo and Yervoy’s benefit was driven by their comparison with Nexavar, because recent analyses have pointed to Lenvima as the more powerful liver cancer med between the two in the first line. BMS' chief medical officer Samit Hirawat, M.D., in an interview with Fierce Pharma, pointed out that the trial was not designed to make comparisons between the Opdivo-Yervoy regimen and each of the two TKIs separately.   It’s worth noting that the control group’s 20.6-month median overall survival (OS) was quite impressive. Back in 2022, Lenvima helped first-line liver cancer patients enrolled in Merck’s LEAP-002 trial live a median of 19 months, which, at the time, was the longest reported for the drug in a phase 3 trial. In that study, Merck and Eisai found the combination of Keytruda and Lenvima failed to significantly beat Lenvima monotherapy on OS. The PD-1/TKI combo’s median OS was 21.2 months. The BMS PD-1/CTLA4 combo of Opdivo and Yervoy now looks to be on a collision course with Roche’s PD-L1/VEGF combo of Tecentriq and Avastin as well as AstraZeneca’s PD-L1/CTLA4 regimen containing Imfinzi and Imjudo. The two existing cocktails in first-line liver cancer got their FDA approvals based on data against Nexavar. In the IMbrave150 trial, Tecentriq and Avastin originally logged a death risk reduction of 42%. But median OS at that time was not reached for the Roche regimen. A post hoc, descriptive analysis with a longer follow-up reported the combo’s median OS at 19.2 months versus 13.4 months for Nexavar. In the HIMALAYA study, Imfinzi and Imjudo showed a median OS of 16.4 months versus 13.8 months for Nexavar. The AZ regimen’s death risk reduction was 22%. Besides the Big Pharma players, Elevar Therapeutics and partner Jiangsu Hengrui Pharma are looking to introduce their anti-PD-1/VEGFR combo of camrelizumab and rivoceranib in first-line liver cancer. The two partners’ applications were recently rejected by the FDA because of manufacturing and clinical trial inspection problems. In the CARES-310 study, the Elevar/Hengrui combo delivered 22.1 months of median OS versus 15.2 months for Nexavar at an interim analysis. The experimental regimen was linked to a death risk reduction of 38%.  At the final OS analysis, the Elevar/Hengrui regimen’s median OS reached 23.8 months, although its death risk reduction fell to 36%, according to results shared at ASCO’s 2024 annual meeting. It would be difficult to compare BMS’ latest results with the others given differences in their trial populations, follow-up time and the comparator arm. When AZ released the HIMALAYA data in early 2022, the British pharma touted the Imfinzi-Imjudo duo’s three-year OS rate, 31%, as unprecedented. Now, Opdivo and Yervoy have broken that record as 38% of patients who took the combo were still alive after three years, versus 24% for Nexavar, in CheckMate-9DW. Doctors will select treatment based on the patient’s characteristics and each regimen’s own profile, Hirawat said. The Opdivo-Yervoy combo can obviously help patients who can’t tolerate Avastin, although Hirawat argued that the pure immunotherapy regimen can attract beyond those patients. “One of the things that we’re seeing is that, as we follow these patients longer and longer, the tail end of the curve is flattening out,” Hirawat said of the survival curves seen with the Opdivo-Yervoy regimen. “So patients who benefit can benefit for a very long time.”

Phase 3 CARES-310 study found combination of camrelizumab and rivoceranib continued to show sustained long-term survival compared with sorafenib as a first-line treatment for uHCC Final analysis reported the longest median overall survival for any treatment in a global Phase 3 trial in uHCC Combination is the only uHCC therapy to increase median overall survival to approximately two years with greater than one in three patients alive at three years FORT LEE, N.J., May 30, 2024 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., today announced the landmark overall survival (OS) analysis of camrelizumab and rivoceranib as a first-line treatment for unresectable hepatocellular carcinoma (uHCC) will be presented at an in-person poster presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1. The abstract can be viewed at asco.org/abstracts. “The CARES-310 final OS analysis confirmed statistically superior and clinically meaningful survival improvement with a manageable safety pro the combination of camrelizumab and rivoceranib as a first-line treatment for patients suffering from unresectable hepatocellular carcinoma,” said Saeho Chong, Elevar chief executive officer. “These data confirm that the novel combination therapy represents a clinically differentiated improvement to the standard of care in first-line treatments for uHCC.” “The CARES-310 landmark analysis reported the longest median overall survival for any treatment in a global Phase 3 trial in the uHCC setting,” said Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The combination of camrelizumab and rivoceranib shows distinct promise to advance the standard of care for patients suffering with unresectable hepatocellular carcinoma.” The interim analysis of CARES-310 OS was completed after data cut-off on Feb. 8, 2022. For the final analysis, 16 months later, camrelizumab + rivoceranib continued to show clinically meaningful survival improvement compared with sorafenib, with manageable safety profile. The extended follow-up further confirmed the favorable benefit-to-risk pro camrelizumab + rivoceranib, supporting it as a potential new first-line treatment option for uHCC. In the final analysis, median OS was significantly prolonged with camrelizumab + rivoceranib vs. sorafenib (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio 0.64 [95% CI 0.52-0.79]; 1-sided p < 0.0001). OS rate with camrelizumab + rivoceranib vs. sorafenib was 49.0% vs. 36.2% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with camrelizumab + rivoceranib were generally consistent across subgroups, regardless of geographical region, race and etiology. CARES-310 was the first trial to demonstrate significant progression-free survival (PFS) and overall survival benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. ASCO 2024 CARES-310 Landmark Overall Survival In-Person Presentation The in-person poster presentation (abstract number 4110), titled “Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the Phase 3 CARES-310 study,” will be presented June 1 from 1:30 p.m. to 4:30 p.m. CT during the poster session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary. The abstract can be viewed at: asco.org/abstracts. Additional ASCO 2024 CARES-310 Online Publication Additional data from CARES-310 will be available as an online publication. Abstract number e16197 is titled: “Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.” The abstract can be viewed at: asco.org/abstracts. 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. About CARES-310 CARES-310 (NCT03764293) was a randomized, open-label, international Phase 3 study, which included 543 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Patients were randomized 1:1 to receive the combination of camrelizumab + rivoceranib or sorafenib (400 mg orally twice daily), a standard-of-care first-line multi-kinase inhibitor treatment for uHCC. Camrelizumab was administered intravenously (190 mg) every two weeks and rivoceranib was administered orally (250 mg) once daily. The study was conducted at 95 study sites across 13 countries/regions, in which systemic treatment for uHCC independent of etiology, rivoceranib plus camrelizumab demonstrated statistically significant and clinically meaningful prolonged overall survival and progression-free survival, and improved overall response rate versus sorafenib. The co-primary endpoints were overall survival and progression-free survival. Secondary endpoints included objective response rate and duration of response. About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to 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, etc.) 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), in combination with rivoceranib as a treatment for uHCC (first-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. About Rivoceranib Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), 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 currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf®). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety pro other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan®. About Elevar Therapeutics Elevar Therapeutics, Inc. is a fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. With expertise rooted in oncology, Elevar is focused on identifying and developing promising medicines for complex yet under-treated health conditions across a range of therapeutic areas. Elevar’s lead proprietary drug candidate is rivoceranib. Elevar is headquartered in New Jersey, with offices in South Korea. Additional information is available at ElevarTherapeutics.com. Media Contact: Jeanette Bressi Head, Corporate Communications, Elevar Therapeutics jbressi@elevartherapeutics.com 609-439-3997 Investor Relations Contact: Ashley R. Robinson, LifeSci Advisors, LLC arr@lifesciadvisors.com