ShanghaiJune 10, 2026 /PRNewswire/ — Hengrui Medicine presented key data from the national multicenter, randomized, controlled, Phase III study SHR-1210-III-336 (CARES-336 study) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in an oral presentation. The study evaluated camrelizumab combined with apatinib (the “dual-ai” regimen) plus transarterial chemoembolization (TACE) versus TACE alone in unresectable hepatocellular carcinoma (uHCC). For the first time, Phase III high-level evidence confirmed that the “dual-ai” regimen combined with TACE provides significant survival benefits in treating uHCC [1], drawing high attention in the international liver cancer field.
The study was co-led by Academician Fan Jia from Zhongshan Hospital, Fudan University, and Professor Qin Shu-kui from Nanjing Tianyinshan Hospital, China Pharmaceutical University, with participation from 34 centers nationwide. Results showed that compared with TACE alone, uHCC patients receiving TACE combined with the “dual-ai” regimen achieved clinically meaningful and statistically significant improvements in progression-free survival (PFS), significantly reducing the risk of disease progression and death [1].
2026 ASCO Congress Site: Professor Peng Tao from the First Affiliated Hospital of Guangxi Medical University Reports Latest Results of CARES-336 Study
Mechanistic Synergy of Targeted Therapy, Immunotherapy, and Intervention
Treatment for intermediate-advanced unresectable liver cancer has long relied on TACE alone, but its overall survival benefits face clear limitations. This regimen selected the “PD-1 + VEGFR TKI” systemic therapy approach, which already had a positive Phase III foundation in first-line advanced treatment from CARES-310 [2-3], and was supported by robust data validated through the Phase II CARES-005 study [4]. Combining this mature systemic regimen with TACE offers a coherent and clear evidence chain, making it easier for domestic physicians to understand and adopt.
From a pathophysiological perspective, the local hypoxic microenvironment induced by TACE embolization leads to a compensatory surge in pro-angiogenic factors such as vascular endothelial growth factor (VEGF), promoting tumor neovascularization and micrometastasis. Additionally, hypoxic stress upregulates PD-L1 expression on tumor cells, mediating immune evasion [5].
The study’s design concept involves introducing apatinib (a highly selective small-molecule VEGFR-2 TKI) to inhibit neovascularization and achieve vascular normalization, improving the local tumor immune microenvironment. This is then combined with camrelizumab (a PD-1 inhibitor) to relieve T-cell immunosuppression. Ultimately, systemic therapy synergizes with TACE-induced massive release of tumor antigens, creating a potent “1 + 1 > 2” synergistic anti-tumor effect [6].
Investigator Perspectives and Clinical Significance
As one of the lead investigators of the study, Academician Fan Jia noted in an exclusive interview during the ASCO conference that the release of the CARES-336 study represents a milestone for the diagnosis and treatment of unresectable hepatocellular carcinoma both domestically and internationally.
This study completes the full-cycle evidence chain for the “dual-ai” regimen: CARES-310 drove its approval for first-line advanced indications; CARES-009 was included in the 2026 edition of the “Guidelines for the Diagnosis and Treatment of Primary Liver Cancer” as Level 1 evidence, Grade A recommendation; CARES-005 provided preliminary groundwork for the “dual-ai” plus TACE regimen; and this study fills the gap in local plus systemic therapy with Phase III evidence, achieving full-scenario coverage for the “dual-ai” regimen in perioperative, intermediate-stage combination, and advanced first-line settings.
As an innovative, domestically developed original drug, the “dual-ai” regimen benefits from production capacity and supply chains deeply rooted in China, offering high clinical accessibility. In recent years, China’s drug review and medical insurance policies have strongly supported local innovations with clear evidence value. Based on the breakthrough results of this combination regimen, its marketing application for this indication has been formally accepted by the National Medical Products Administration (NMPA). The detailed data presented at this ASCO further solidifies its evidence foundation. It is foreseeable that, with policy support, this regimen will not only rapidly fill the clinical gap in initial combination therapy for intermediate-advanced liver cancer in China but also drive revisions to authoritative liver cancer treatment guidelines, such as those from CSCO, translating high-level research outcomes into practical, standardized clinical decision-making protocols for hospitals at all levels across China.
About the SHR-1210-III-336 Study (CARES-336 Study)
This study is a randomized, controlled, open-label, multicenter Phase III clinical trial evaluating the efficacy and safety of camrelizumab and apatinib mesylate combined with TACE versus TACE alone in patients with unresectable hepatocellular carcinoma. Co-led by Academician Fan Jia from Zhongshan Hospital, Fudan University, and Professor Qin Shu-kui from Nanjing Tianyinshan Hospital, China Pharmaceutical University, as principal investigators, the study involved 34 centers nationwide and enrolled 423 patients. The primary efficacy endpoint was progression-free survival (PFS) assessed by a blinded independent review committee (BIRC). Secondary efficacy endpoints included overall survival (OS), investigator-assessed PFS, BIRC- and investigator-assessed objective response rate (ORR), disease control rate (DCR), and duration of response (DoR). Interim analysis results showed that, compared with TACE alone, the camrelizumab plus apatinib mesylate and TACE group achieved a statistically significant and clinically meaningful improvement in BIRC-assessed PFS, with a trend toward OS benefit observed. This combination therapy is expected to become a new clinical treatment option for patients with unresectable hepatocellular carcinoma.
About Unresectable Hepatocellular Carcinoma
Primary liver cancer is one of the most common malignant tumors globally, with hepatocellular carcinoma (HCC) accounting for 90% of pathological types [7]. According to GLOBOCAN 2022 data, there are over 860,000 new cases and over 750,000 deaths from liver cancer worldwide each year, ranking it third among global causes of cancer death [8]. China is a high-incidence area for liver cancer, with 367,700 new cases and 316,500 deaths in 2022 [9]. Treatment for HCC varies by disease stage. TACE is widely used across various stages of liver cancer in China and has become the standard treatment for unresectable intermediate-stage HCC patients. However, repeated TACE treatments can cause liver function damage, limiting its clinical application and preventing some patients from benefiting. The efficacy of PD-1/PD-L1 antibodies combined with anti-angiogenic targeted drugs has been validated in first-line treatment for advanced HCC. Mechanistically, this combination therapy can inhibit potential tumor immune evasion and tumor neovascularization induced by TACE, producing synergistic effects [10]. The combination of PD-1/PD-L1 antibodies, anti-angiogenic targeted drugs, and TACE is expected to improve clinical outcomes for patients with unresectable intermediate-stage HCC.
About Camrelizumab and Apatinib
Camrelizumab for injection is a humanized PD-1 monoclonal antibody independently developed by the company. It binds to the human PD-1 receptor and blocks the PD-1/PD-L1 pathway, restoring the body’s anti-tumor immunity, thereby forming the basis of cancer immunotherapy. Camrelizumab has high affinity for PD-1 and significantly extends overall survival in studies of various solid tumors [11-13]. Camrelizumab was approved for marketing in May 2019 and has since received multiple indications in China, covering lung cancer, liver cancer, esophageal cancer, nasopharyngeal cancer, and cervical cancer, making it the leading domestic PD-1 product in terms of approved indications and covered tumor types.
Apatinib mesylate is a small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), independently developed by the company. It was approved for marketing in October 2014. Currently, apatinib mesylate tablets have received four indications in China.
About Hengrui Oncology
Hengrui Oncology is one of the core strategic business segments of Hengrui Medicine. As a pioneering sector in innovation transformation, Hengrui Oncology has achieved technological breakthroughs and international expansion. Since the 1970s, Hengrui has built an anti-tumor drug R&D system from scratch, completing key accumulation from generics to independent R&D. It launched its first anti-tumor drug in 1987, laying a solid foundation for development. In 2014, the world’s first oral small-molecule targeted drug for advanced gastric cancer, apatinib mesylate tablets (Aitan®), was successfully launched, marking a milestone breakthrough in original innovation for Hengrui Oncology. As of the first quarter of 2026, Hengrui Oncology has launched 14 independently developed Class 1 innovative drugs in China, with multiple products receiving U.S. Orphan Drug and Fast Track designations. Currently, Hengrui Oncology has formed a systematic layout covering seven major high-incidence cancer types, tumor supportive care, and multiple areas of significant unmet clinical needs. Leveraging its global R&D system and diversified international collaborations, Hengrui Oncology is accelerating its leap from “Chinese innovation” to “global innovation,” providing more precise, accessible, and higher-quality treatment options for cancer patients worldwide.
References:
- Weidong Jia, et al. Camrelizumab (C) plus rivoceranib (R) with transarterial chemoembolization (TACE) vs TACE alone in unresectable hepatocellular carcinoma (uHCC): a randomized, phase 3 trial. 2026 ASCO Oral 4001.
- Nordenstedt H, White DL, El-Serag HB. The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis. 2010;42 Suppl 3(Suppl 3): S206-S214.
- Viveiros P, Riaz A, Lewandowski RJ, Mahalingam D. Current State of Liver-Directed Therapies and Combinatory Approaches with Systemic Therapy in Hepatocellular Carcinoma (HCC). Cancers (Basel). 2019;11(8):1085. Published 2019 Jul 31
- Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naïve patients with advanced non-squamous non-small-cell lung cancer (CameL): a andomized, open-label, multicentre, phase 3 trial. Lancet Respir Med. 2021 Mar;9(3):305-314.