Toripalimab Combo May Improve Survival Vs Sorafenib in Advanced HCC

In the open-label, multicenter phase 3 HEPATORCH trial (NCT04723004), 326 patients were randomly assigned to receive treatment with toripalimab/bevacizumab or sorafenib.

Combining toripalimab-tpzi (Loqtorzi) with bevacizumab (Avastin) as frontline treatment for patients with advanced hepatocellular carcinoma (HCC) reached the predefined efficacy boundary for the primary end points of overall survival (OS) and progression-free survival (PFS), according to topline results from the phase 3 HEPATORCH trial (NCT04723004).¹

Findings indicate that the toripalimab-based regimen may significantly improve OS and PFS compared with sorafenib (Nexavar) in this population. Additionally, investigators reported that the experimental combination may elicit benefits with respect to secondary end points, including objective response rate (ORR) and time to progression.

Investigators identified no new safety signals in the HEPATORCH trial. The safety profile of toripalimab was comparable with prior reports of the agent.

Investigators will present additional results from the HEPATORCH trial at a future international academic conference. Developers also plan to submit a supplemental biologics license application soon to regulatory agencies in support of the toripalimab-containing regimen.

“Currently, the combination of immune checkpoint inhibitors and antiangiogenesis-targeted therapies has become a vital first-line treatment for advanced liver cancer. The phase 3 HEPATORCH clinical study evaluating toripalimab combined with bevacizumab achieved its primary end point, potentially offering a new treatment option with better survival benefits for [patients with] advanced liver cancer,” lead trial investigator Jia Fan, president at Zhongshan Hospital and academic member from the Chinese Academy of Sciences, said in the press release.¹

In the open-label, multicenter phase 3 HEPATORCH trial, 326 patients were randomly assigned to receive treatment with toripalimab/bevacizumab or sorafenib.² Treatment in the experimental arm consisted of intravenous toripalimab at 240 mg every 3 weeks plus intravenous bevacizumab at 15 mg/kg every 3 weeks. Patients assigned to the control arm received sorafenib at 400 mg orally twice a day.

The trial’s primary end points were PFS based on RECIST v1.1 criteria and OS. Secondary end points included ORR, duration of response, disease control rate, time to progression, adverse effects, association between tumor mutation burden and treatment efficacy, and serum levels and anti-drug antibody presence in the experimental arm.

Patients aged 18 to 75 years old with histologically or cytologically confirmed HCC and unresectable Barcelona Clinic Liver Cancer stage B or C disease were eligible for enrollment on the trial. Other requirements for enrollment included having no prior systemic therapy, at least 1 measurable lesion based on RECIST v1.1 guidelines, Child-Pugh class A disease without hepatic encephalopathy, an ECOG performance status of 0 or 1, a predicted life expectancy of 12 weeks or longer, and adequate organ function.

Those with mixed cell carcinoma, sarcomatoid HCC, hepatic fibrolamellar carcinoma, or a history of malignancy apart from HCC within 5 years before screening were ineligible for study entry. Patients were also unable to enroll if they had prior treatment with anti–PD-1 or anti–PD-L1 agents; uncontrolled pericardial effusion, pleural effusion, or moderate or severe pleural effusion at screening; serious cardiovascular or cerebrovascular diseases; central nervous system metastases; prior interstitial lung disease or non-infectious pneumonia; or prior receipt of allogenic stem cell or solid organ transplantation.

“The incidence and mortality rates of hepatocellular carcinoma in China have remained consistently high, posing a serious threat to public health,” Jianjun Zou, MD, PhD, general manager and chief executive officer of Junshi Biosciences, the developers of toripalimab, stated in the press release.² “Moving forward, we will actively communicate with regulatory authorities to expedite the approval of relevant indications, and we hope our efforts will benefit more patients with advanced liver cancer.”

References

1. Junshi Biosciences announces phase 3 study of toripalimab combined with bevacizumab for the first-line treatment of advanced hepatocellular carcinoma meets primary endpoint. News release. Shanghai Junshi Biosciences, Co. Ltd. June 12, 2024. Accessed June 13, 2024. https://tinyurl.com/4cha7f9s
2. Evaluate the safety and efficacy of toripalimab combined with bevacizumab versus sorafenib therapy for HCC. ClinicalTrials.gov. Accessed June 13, 2024. https://tinyurl.com/3xv33d8b