Perioperative Toripalimab Plus Chemotherapy Meets EFS End Point in NSCLC

Perioperative treatment with the combination of toripalimab plus platinum-containing doublet chemotherapy, followed by toripalimab monotherapy as consolidation therapy after surgery, significantly extended event-free survival compared with chemotherapy plus placebo in patients with operable non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 Neotorch trial (NCT04158440).¹

A prespecified interim analysis of the trial also showed that safety data for toripalimab were consistent with the known toxicity profile of the agent, and no new safety signals identified.

Toripalimab is an anti–PD-1 monoclonal antibody designed to inhibit PD-1 interactions with its ligands, PD-L1 and PD-L2. The drug also enhances receptor internalization to promote the immune system’s ability to attack and kill tumor cells.

The ongoing randomized, double-blind, placebo-controlled, multicenter Neotorch trial is evaluating toripalimab in combination with platinum-containing doublet chemotherapy vs placebo plus platinum-containing doublet chemotherapy for patients with operable NSCLC. Patients are required to be aged between 18 and 70 years with treatment-naïve, histologically confirmed, resectable stage II, IIIA, or IIIB NSCLC.² Other key eligibility criteria include measurable lesions per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and good organ function.

Exclusion criteria include the presence of locally advanced, unresectable, or metastatic disease; NSCLC involving superior sulcus, large cell neuroendocrine carcinoma, or sarcomatoid tumor; known EGFR sensitive mutations or ALK translocation; or a history of or ongoing pneumonitis/interstitial lung disease requiring steroid treatment.

Enrolled patients are being randomly assigned to received 240 mg of intravenous (IV) toripalimab or placebo plus 75 mg/m² of IV cisplatin, IV carboplatin at area under the curve 5, and 500 mg/m² of IV pemetrexed (Alimta) every 3 weeks. Each agent is administered on day 1 of each cycle, and perioperative treatment consists of 4 cycles. Patients with nonsquamous NSCLC are being given 175 mg/m² of IV paclitaxel and 60 mg/m² to 75 mg/m² of IV docetaxel every 3 weeks. After surgery, patients will receive 240 mg of IV toripalimab or placebo every 3 weeks for 13 cycles.

Along with EFS, major pathological response rate is serving as a co-primary end point. Secondary end points consist of pathological complete response rate, disease-free survival, and overall survival.

In China, toripalimab is currently approved for unresectable or metastatic melanoma after failure of standard systemic therapy; recurrent or metastatic nasopharyngeal cancer after failure of at least 2 lines of prior systemic therapy; locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy; in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic nasopharyngeal cancer; in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma; and in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation–negative and ALK mutation­–negative, unresectable, locally advanced or metastatic nonsquamous NSCLC.

In July 2022, the FDA accepted for review a biologics license application resubmission for toripalimab both in combination and as monotherapy for patients with advanced recurrent or metastatic nasopharyngeal carcinoma.³

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. http://bit.ly/3ZLBrtW
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 announce FDA acceptance of resubmission of BLA for toripalimab for the treatment of nasopharyngeal carcinoma. News release. Coherus Biosciences. July 6, 2022. Accessed January 18, 2023. https://bit.ly/3nKM2Dm