NMPA Accepts sNDA for Toripalimab Plus Bevacizumab as Frontline Therapy in Advanced HCC

Professor Jia Fan

The National Medical Products Administration has accepted for review the supplemental new drug application (sNDA) for toripalimab (Tuoyi) for use in combination with bevacizumab (Avastin) for the frontline treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC).¹

The sNDA is based on findings from the phase 3 open-label HEPATORCH trial (NCT04723004), in which the combination of toripalimab and bevacizumab produced a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) vs sorafenib (Nexavar) as first-line treatment in patients with locally advanced or metastatic HCC who could not be radically cured.^1,2

“Due to the hidden onset of HCC, most domestic patients have already missed the opportunity for radical surgery at the time of initial diagnosis. The HEPATORCH study results show that first-line treatment of advanced HCC with toripalimab combined with bevacizumab offers significant survival benefits,” Professor Jia Fan, principal investigator and academician at the Chinese Academy of Sciences and president of Zhongshan Hospital, stated in a news release.¹ “The study also reaffirms the efficacy of combining immunosuppressants with anti-angiogenesis–targeting drugs for advanced HCC. We eagerly await the approval of this therapy that combines toripalimab with bevacizumab, which will provide new treatment options for advanced HCC patients in China!”

In June 2024, the developer of toripalimab, Junshi Biosciences, in addition to announcing that HEPATORCH met both of its primary end points, noted that the combination also led to improvements in objective response rate (ORR) and time to progression, which served as secondary end points of the trial.

To be eligible for enrollment in the HEPATORCH trial, patients between the ages of 18 and 75 years must have received a histological or cytological diagnosis of HCC or a clinical diagnosis of HCC in cirrhotic patients according to the American Association for the Study of Liver Diseases guideline. In addition, patients must have had unresectable BCLC B or C disease; no prior exposure to systemic therapy for HCC; at least 1 measurable lesion per RECIST v1.1 criteria; Child-Pugh class A liver disease with no history or hepatic encephalopathy; an ECOG performance status of 0 or 1; a life expectancy of at least 12 weeks; and adequate main organ function.³

Per the trial design, patients underwent random assignment in a 1:1 fashion to receive 240 mg of toripalimab as an intravenous infusion every 3 weeks plus 15 mg/kg of bevacizumab every 3 weeks as a continuous infusion; or 400 mg of oral sorafenib twice daily.

In addition to the primary end points of PFS and OS, investigators are evaluating ORR, duration of response, disease control rate, time to progression, the incidence of adverse effects (AEs) and serious AEs as assessed by the Common Terminology Criteria for Adverse Events version 5.0, the correlation between tumor mutation burden and efficacy of the combination, and serum levels and incidence of anti-drug antibodies with the combination.

According to the news release, the safety profile of toripalimab in the pivotal trial was consistent with its established profile. More details are expected at an upcoming international conference.¹

“I’m delighted to see the successful submission of the sNDA for toripalimab’s eleventh indication,” Dr Jianjun Zou, general manager and chief executive officer of Junshi Biosciences, said in the news release. “Since receiving marketing approval in 2018 as the first domestically developed anti–PD-1 monoclonal antibody, toripalimab has targeted the unmet needs of cancer patients in China and even internationally. As of now, it has been approved for 10 indications in 7 cancer types, many of which are exclusive indications. This sNDA is toripalimab’s first indication in liver cancer, and once again, toripalimab is demonstrating its ‘broad-spectrum’ when battling cancer. Going forward, we will actively communicate with regulatory authorities to speed up the approval of this indication, so that more advanced liver cancer patients can benefit from our innovative therapy.”

References

1. Junshi Biosciences announces the acceptance of the supplemental new drug application for toripalimab combined with bevacizumab for the first-line treatment of advanced hepatocellular carcinoma. News release. Junshi Biosciences. July 17, 2024. Accessed July 18, 2024. https://www.globenewswire.com/news-release/2024/07/18/2915001/0/en/Junshi-Biosciences-Announces-the-Acceptance-of-the-Supplemental-New-Drug-Application-for-Toripalimab-Combined-with-Bevacizumab-for-the-First-Line-Treatment-of-Advanced-Hepatocellul.html
2. Junshi Biosciences announces phase 3 study of toripalimab combined with bevacizumab for the first-line treatment of advanced hepatocellular carcinoma meets primary end point. News release. Junshi Biosciences. June 11, 2024. Accessed July 18, 2024. https://www.globenewswire.com/news-release/2024/06/12/2897253/0/en/Junshi-Biosciences-Announces-Phase-3-Study-of-Toripalimab-Combined-with-Bevacizumab-for-the-First-line-Treatment-of-Advanced-Hepatocellular-Carcinoma-Meets-Primary-Endpoint.html
3. Evaluate the safety and efficacy of toripalimab combined with bevacizumab versus sorafenib therapy for HCC. ClinicalTrials.gov. Updated August 14, 2023. Accessed July 18, 2024. https://www.clinicaltrials.gov/study/NCT04723004