China’s NMPA Accepts sNDA for First-Line Toripalimab Plus Chemo in ES-SCLC

China’s National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) seeking the approval of toripalimab in combination with platinum-based chemotherapy for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).¹

The sNDA is supported by data from the phase 3 EXTENTORCH trial (NCT04012606), which demonstrated that the combination of toripalimab and a chemotherapy regimen consisting of etoposide plus cisplatin or carboplatin improved both progression-free survival (PFS) and overall survival (OS) vs platinum-based chemotherapy alone, meeting the primary end points of the study. Full findings will be presented at an upcoming medical meeting.

“SCLC presents with less noticeable early symptoms, and due to its rapid tumor proliferation and high malignancy, many patients are already late-stage or have systemic metastasis at the time of their initial diagnosis,” principal study investigator Ying Cheng, MD, of the Department of Thoracic Medical Oncology at Jilin Cancer Hospital in Jilin, China, and vice president of the Chinese Society of Clinical Oncology, stated in a news release. “For those diagnosed with ES-SCLC, their average survival time is only about a year. However, EXTENTORCH has successfully confirmed that combining toripalimab with chemotherapy as a first-line treatment for ES-SCLC can significantly improve patients’ PFS and OS. These results may offer a broader range of more effective treatment options for ES-SCLC patients.”

Toripalimab is the first PD-1 inhibitor to meet primary end points for both OS and PFS in a phase 3 study for the first-line treatment of patients with ES-SCLC, according to Junshi Biosciences.

The randomized, double-blind, placebo-controlled, multicenter EXTENTORCH study enrolled approximately 420 patients at least 18 years of age with previously untreated, histologically or cytologically confirmed ES-SCLC per the Veterans Administration Lung Study Group staging system.2 Patients were required to be treatment free for at least 6 months following any curative-intent chemotherapy or radiation given for limited-stage SCLC. Other key inclusion criteria consisted of measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, an estimated life expectancy of at least 8 weeks, and adequate hematologic and end organ function. Notably, patients with asymptomatic brain metastases who received prior treatment were allowed to enroll.

Patients were excluded if they had any prior systemic treatment for ES-SCLC, received any prior treatment with a CD137 agonist or an immune checkpoint inhibitor, had active or untreated central nervous system metastases, had cancerous meningitis, had uncontrolled or symptomatic hypercalcemia, or had spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression that was not clinically stable for at least 1 week prior to enrollment.

Investigators randomly assigned patients 1:1 to receive toripalimab or placebo in combination with etoposide plus cisplatin or carboplatin for 4 to 6 cycles. Patients then received maintenance therapy with toripalimab or placebo alone until disease progression, unacceptable toxicity, or other discontinuation criteria were met.¹

Along with the primary end points of OS and investigator-assessed PFS, secondary end points consisted of PFS per blinded independent review committee, objective response rate, duration of response, disease control rate, time to response, 1- and 2-year OS rate, 6-month PFS rate, and safety.²

Regarding safety, the toxicity profile of toripalimab was consistent with data from previous studies, and no new safety signals were identified.¹

“It was my great pleasure to witness the successful sNDA submission for toripalimab’s 10th indication,” Jianjun Zou, MD, PhD, president of Global Research and Development at Junshi Biosciences, said in a news release. “Since its clinical approval in late 2015, toripalimab has been addressing the unmet medical needs of patients in China and worldwide. Over 40 registered clinical trials have been conducted to further investigate toripalimab, which has continued to demonstrate stable and powerful antitumor activity across various tumor types. In lung cancer alone, toripalimab has been involved in 3 successful large-scale phase 3 clinical trials encompassing diverse subtypes and stages of disease progression. We will work diligently on marketing applications relevant to the indication and strive to help more cancer patients with our innovative therapies.”

References

1. Junshi Biosciences announces acceptance of the supplemental new drug application for toripalimab as the first-line treatment of extensive-stage small cell lung cancer. News release. Junshi Biosciences. July 19, 2023. Accessed July 20, 2023. https://www.globenewswire.com/news-release/2023/07/20/2707845/0/en/Junshi-Biosciences
2. Toripalimab in combination with platinum plus etoposidein patients with extensive-stage small cell lung cancer. ClinicalTrials.gov. Updated September 30, 2020. Accessed July 20, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04012606