Toripalimab Plus Platinum Doublet Chemotherapy Prolongs EFS in Resectable NSCLC

The perioperative use of toripalimab in combination with platinum-based doublet chemotherapy achieved event-free survival (EFS) improvement in Chinese patients with operable non–small cell lung cancer (NSCLC), according to an update from the phase 3 Neotorch trial (NCT04158440).¹

According to Junshi Biosciences, Neotorch is the first registered phase 3 study to demonstrate a an EFS benefit with immunotherapy for lung cancer. In addition, the safety of toripalimab in the study was consistent with the known risks of the therapy, and no new safety signals were observed during the interim analysis. The results will be shared with global regulatory authorities.

In the randomized, double-blind, placebo-controlled, multicenter Neotorch study, 500 patients with resectable, stage II-III NSCLC will receive toripalimab 240 mg via intravenous infusion plus platinum-based chemotherapy doublet or placebo plus platinum-based chemotherapy doublet. The chemotherapy agents utilized in the study included cisplatin, carboplatin, pemetrexed, paclitaxel, and docetaxel.²

Along with EFS, the study is evaluating major pathological remission rate as a primary end point, and both outcomes are assessed by blind independent pathology review committee and investigators. The secondary end points of the study include pathological complete response rate, EFS assessed by an independent review committee, disease-free survival, overall survival, and safety. Other outcomes being looked at in Neotorch are safety, biomarkers, pharmacokinetics, and immunogenicity.¹

The patients being enrolled in the study are males and females aged 18 to 70 years with treatment-naïve disease that is histologically confirmed. All patients are required to have measurable lesions, an ECOG performance status of 0-1, adequate organ function, and a good pulmonary function test.

Noetorch excludes patients with unresectable disease. Patients with EGFR mutation or ALK alterations, and those previously treatment with systemic antitumor therapy for early NSCLC are also excluded. The study also does not allow enrollment of patients with certain disease or infections that may interfere with study treatment. Some of the comorbidities that lead to patient exclusion are active tuberculosis, grade 2 or higher peripheral neuropathy, cirrhosis, and cardiovascular disease.

Toripalimab is an anti-PD-1 monoclonal antibody that is currently not FDA approved. However, the FDA is considering a biologics license application for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced, recurrent, or metastatic nasopharyngeal carcinoma. It was recently announced that ta decision on the BLA was postponed due travel restrictions. Travel is needed so that FDA officials can inspect the manufacturing facility.³

The BLA is supported by findings from the JUPITER-02 study (NCT03581786) and the POLARIS-02 study (NCT02915432) in which toripalimab showed PFS improvement and better objective response rate compared with chemotherapy alone, as well as a manageable safety profile. Specifically, the median progression-free survival observed in the toripalimab arm was 11.7 months (95% CI, 11.0-not evaluable [NE]) per blinded independent review committee assessment vs 8.0 months (95% CI, 7.0-9.5) in the chemotherapy alone arm (stratified HR, 0.52; 95% CI, 0.36-0.74; P =.0003). The ORR observed with toripalimab was 20.5% (95% CI, 15.0%-27.0%).

“Although toripalimab’s BLA review process has been impacted by the COVID-19 pandemic, we believe the impact is temporary,” said Sheng Yao, PhD, senior vice president of Junshi Biosciences, in the press release.¹ “Together with our partner Coherus, we are working with the FDA to expedite the facility inspection so it may be conducted safely as soon as possible in order to provide NPC patients with a treatment that has been demonstrated to be safe and effective. Our production operations are well prepared for the inspection.”

_REFERENCES:

_{1. Junshi Biosciences announces toripalimab as perioperative treatment for operable NSCLC patients met primary endpoint in phase 3 clinical study. News release. Junshi Biosciences. January 17, 2023. Accessed January 18, 2023. https://bit.ly/3XJV1VD}

_{2. Phase III study of toripalimab versus placebo plus chemotherapy in resectable NSCLC. Clinicaltrials.gov. Updated November 3, 2022. Accessed January 18, 2023. https://clinicaltrials.gov/ct2/show/NCT04158440}

_{3. Coherus and Junshi Biosciences share update on the FDA review of the biologics license application (BLA) for toripalimab as treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). News release. December 24, 2022. Accessed January 18, 2023. https://bit.ly/3WlZn4T}

_{3. Phase III study of toripalimab versus placebo plus chemotherapy in resectable NSCLC. Clinicaltrials.gov. Updated November 3, 2022. Accessed January 18, 2023. https://clinicaltrials.gov/ct2/show/NCT04158440}

_{4. Mai H, Chen Q, Chen D, et al. Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. Presented at: American Association for Cancer Research 2022 Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT226.}

_{5. Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase ii clinical trial (POLARIS-02). J Clin Oncol. 2021; 39(7): 704-712. doi:10.1200/JCO.20.0271}