Chinese Regulators Accept sBLA for Toripalimab/Chemo in Advanced TNBC

China’s National Medical Products Administration has accepted a supplemental new drug application (sNDA) for toripalimab (Tuoyi) in combination with albumin-bound paclitaxel for the treatment of patients with untreated metastatic or recurrent PD-L1–positive triple-negative breast cancer (TNBC), according to a press release from Shanghai Junshi Biosciences Co., Ltd.¹

Investigators will present detailed results from the phase 3 TORCHLIGHT trial as part of a late-breaking abstract at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The agency accepted the sBLA based on supporting data from the phase 3 TORCHLIGHT study (NCT04085276), in which investigators compared the safety and efficacy of toripalimab plus paclitaxel with placebo plus paclitaxel in those with stage IV or recurrent TNBC.

“In our TORCHLIGHT study, we combined chemotherapy with an immune checkpoint inhibitor, which resulted in significantly prolonged PFS in patients [with TNBC], along with other significant survival benefits,” principal investigator Zefei Jiang, MD, professor in the Department of Oncology at the Chinese People’s Liberation Army General Hospital, said in the press release. “I am delighted to see the acceptance of the NDA for toripalimab in combination with chemotherapy for the treatment of advanced TNBC.”

An interim analysis conducted in February 2023 indicated that the toripalimab-based regimen significantly prolonged progression-free survival (PFS) compared with the placebo-based regimen in patients with PD-L1–positive disease, thus meeting the pre-defined efficacy boundary for the trial’s primary end point.2 Additionally, toripalimab plus placebo improved overall survival (OS) in PD-1–positive patients and the overall population regardless of PD-1 status. Investigators identified no new safety signals during the trial, and the safety profile of toripalimab was consistent with previous reports of checkpoint inhibitors.

“The TNBC subtype of breast cancer is the most aggressive and has the worst prognosis,” Jiang said at the time of the interim analysis. “[Patients with] advanced TNBC have limited survival rates and lack effective treatment methods. Aiming to improve patient survival, a group of Chinese researchers successfully conducted the first phase 3 study on immune-oncology for [patients with] advanced TNBC, even amidst the COVID-19 pandemic, and achieved breakthrough results.

“These results demonstrate that the combined use of the monoclonal antibody, toripalimab, with traditional chemotherapy significantly prolonged the PFS of patients, and this has the potential to become a new standard treatment for patients with an initial diagnosis of stage IV TNBC as well as those with recurrent/metastatic TNBC….”

Investigators will present detailed results from the TORCHLIGHT trial as part of a late-breaking abstract at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The multi-center, randomized, open-label phase 3 TORCHLIGHT study had an actual enrollment of 531 patients who were randomly assigned to receive either 125 mg of intravenous nab-paclitaxel on days 1 and 8 every 3 weeks plus 240 mg of toripalimab intravenously or matched placebo every 3 weeks plus the nab-paclitaxel backbone.

Secondary end points included investigator-assessed PFS, objective response rate, duration of response, disease control rate, OS, and safety and tolerability.

Patients 18 years and older with a histologically confirmed diagnosis of TNBC that is estrogen receptor negative, progesterone receptor negative, or HER2 negative were eligible for enrollment on the trial. Additional inclusion criteria included being eligible to receive taxane monotherapy, receiving a maximum of 1 line of chemotherapy in the metastatic setting, an ECOG performance status of 1 or 0, a life expectancy of at least 12 months, and at least 1 measurable lesion per RECIST v1.1 criteria. Patients also needed to have adequate hematologic and organ function to enroll.

Patients who received prior therapy with a PD-1, PD-L1, PD-L2, or CTLA4 antibody were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had active or untreated brain metastases confirmed via MRI assessment, meningeal carcinomatosis, or active hepatitis B or C.

“We plan to work closely with regulatory authorities to expedite the approval process [for toripalimab plus chemotherapy] and address the unmet needs of countless patients [with TNBC] in China as soon as possible,” Jianjun Zou, MD, PhD, president of Global Research and Development at Junshi Biosciences, concluded.

References

1. Junshi Biosciences announces acceptance of the supplemental NDA for toripalimab in combination with chemotherapy for advanced triple-negative breast cancer. News release. Shanghai Junshi Biosciences Co., Ltd.. May 23, 2023. Accessed May 24, 2023. bit.ly/3BTqYle
2. Junshi Biosciences announces toripalimab in combination with chemotherapy for treatment of advanced triple-negative breast cancer met primary endpoint in phase 3 clinical study. News release. Shanghai Junshi Biosciences Co., Ltd. February 20, 2023. Accessed May 24, 2023. https://yhoo.it/3xHpaK2