China’s NMPA Accepts sNDA for Toripalimab Plus Chemo in Advanced TNBC

The National Medical Products Administration has accepted the supplemental new drug application (sNDA) seeking the approval of toripalimab (Tuoyi) in combination with nab-paclitaxel (Abraxane) in patients with untreated metastatic or recurrent triple-negative breast cancer (TNBC) and a PD-L1 combined positive score (CPS) of at least 1.¹

The application is based on findings from the registrational phase 3 TORCHLIGHT study (NCT04085276).² Topline data from an interim analysis indicated that the addition of toripalimab to chemotherapy resulted in a significant improvement in progression-free survival (PFS) over chemotherapy alone in this population, meeting the primary end point of the trial.

A positive trend toward improved overall survival (OS) was also observed with toripalimab, irrespective of PD-L1 status. Moreover, the toxicity profile of the agent was consistent with what has previously been reported with checkpoint inhibitors. No new signals were reported.

Detailed findings from the trial are slated to be presented during the rapid abstract session at the upcoming ASCO Annual Meeting in June.¹

“In our TORCHLIGHT study, we combined chemotherapy with an immune checkpoint inhibitor, which result in significantly prolonged PFS in [patients with] TNBC, along with other significant survival benefits,” Professor Zefei Jiang, MD, of the Department of Oncology of the Chinese People’s Liberation Army General Hospital, stated in a press release. “I am delighted to see the acceptance of the NDA for [this regimen] for the treatment of advanced TNBC. I eagerly anticipate its approval as it will provide better treatment options for [patients with] TNBC in China!”

The randomized, double-blind, placebo-controlled, multicenter, phase 3 trial enrolled patients with a histologically confirmed diagnosis of TNBC who have not received more than 1 line of chemotherapy in the metastatic setting.³ Patients were required to have a least 1 measurable lesion by RECIST v1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and acceptable hematologic and organ function.

If patients previously received a taxane in the frontline setting, or prior treatment with a PD-1, PD-L1, PD-L2, or CTLA-4 antibody, they were excluded. They also could not have meningeal carcinomatosis, nor could they have hepatitis B or C.

Study participants on the investigative arm were given toripalimab intravenously (IV) at 240 mg every 3 weeks or placebo in combination with IV nab-paclitaxel at 125 mg/m² on days 1 and 8 of each treatment cycle every 3 weeks.

The primary end points of the trial were PFS by blinded independent central review and RECIST v1.1 criteria in the intention-to-treat population, as well as in the subgroup of patients with PD-L1 positivity. Key secondary end points include investigator-assessed PFS in both populations, objective response rate, duration of response, disease control rate, OS, 12-month OS rate, safety, tolerability, and differences in scores of disease- or treatment-related symptoms examined by performance status.

“We at Junshi Biosciences have remained steadfast in our patient-centric approach and successfully collaborated with researchers on the TORCHLIGHT study, which has demonstrated significant improvements in PFS and OS,” Jianjun Zou, MD, PhD, president of global research and development at Junshi Biosciences, added in the press release.¹ “We plan to work closely with regulatory authorities to expedite the approval process and address the unmet needs of countless [patients with] TNBC in China as soon as possible.”

In China, toripalimab has been approved for use in the following 6 indications:

1. Unresectable or metastatic melanoma following progression on standard systemic treatment
2. Recurrent or metastatic nasopharyngeal carcinoma (NPC) following progression on two or more systemic therapies
3. Locally advanced or metastatic urothelial cancer that progressed on platinum-based chemotherapy or within 1 year of neoadjuvant or adjuvant platinum-based chemotherapy
4. In combination with cisplatin plus gemcitabine in patients with untreated locally recurrent or metastatic NPC
5. In combination with paclitaxel plus cisplatin for untreated unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma
6. In combination with pemetrexed plus a platinum in treatment-naïve unresectable, locally advanced, or metastatic nonsquamous non–small cell lung cancer that does not harbor EGFR or ALK mutations

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 23, 2023. https://www.junshipharma.com/en/
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 23, 2023. https://www.junshipharma.com/en/
3. Toripalimab in combination with nab-paclitaxel for patients with metastatic or recurrent triple-negative breast cancer (TNBC) with or without systemic treatment (TORCHLIGHT). ClinicalTrials.gov. Updated March 7, 2023. Accessed May 23, 2023. https://clinicaltrials.gov/ct2/show/NCT04085276