Immunotherapy dominates the first-line treatment landscape for advanced non-small cell lung cancer (NSCLC) that lack any targetable mutation. Pivot trials such as KEYNOTE189, KEYNOTE407, CheckMate 227, CheckMate 9LA, and IMPOWER130, have demonstrated effectiveness of immune checkpoint inhibitors (ICIs), giving doctors a plethora of options for their patients. Furthermore, the advent of immunotherapy treatments has become particularly attractive for patients that are interested in a chemotherapy-free or reduced chemotherapy regimens. Immunotherapy is also not typically associated with myelosuppression, hair loss, and nausea as that seen with traditional chemotherapy, but it does have its own set of grade 3 side effects and need to properly managed and monitored. Utilizing immunotherapy in the first-line can be particularly attractive to doctors because it could allow for platinum doublet therapy instead of docetaxel based therapies if a second-line treatment is needed.
New data presented at 2021 World Conference on Lung Cancer is adding another ICI competitor to the list, with Coherus’s toripalimab meeting its primary endpoint.  Toripalimab is a monoclonal antibody against programed death 1 (PD-1) that was developed to block PD-1 interaction with PD-L1 and PD-L2. It is also believed to support efficient endocytosis of the PD-L1 receptor, allowing for T cells to bypass the tumor PD-L1 and PD-L2 checkpoints. It is currently approved in China for second line treatment of melanoma, urothelial cancer, and nasopharyngeal carcinoma. In the United States, it has fast track designation for melanoma and breakthrough therapy designation for nasopharyngeal carcinoma. [2,3]
The CHOICE-01 trial (NCT03856411), a randomized, double-blind, placebo-controlled Phase III trial, explored the safety and efficacy of toripalimab combined with chemotherapy for patients with advanced NSCLC. A total of 465 patients with advanced NSCLC without EGFR/ALK driver mutations were randomized (2:1) for front-line chemotherapy (paclitaxel plus carboplatin for squamous; pemetrexed plus cisplatin/carboplatin for non-squamous) in combination with either toripalimab or placebo. Crossover to toripalimab was allowed upon disease progression in the placebo group.
As of November 17, 2020, there were 218 progression free survival (PFS) events, with a median follow up time of 7.1 months for toripalimab and 7.0 months for the placebo. Investigator assessed PFS was significantly improved (HR=0.58 [95% CI: 0.44-0.77], P=0.0001), with PFS of 8.3 months in the toripalimab group compared to 5.6 months for the placebo. Additionally, toripalimab had a 1-year survival rate of 32.6% versus only 13.1% in the placebo group. The improvement in PFS was observed in both squamous and non-squamous NSCLC and irrespective of PD-L1 status. Toripalimab treatment also resulted in better objective response rate (ORR) (squamous NSCLC: 68.7% vs. 58.9%; non-squamous NSCLC: 58.6% versus 26.5%) and median duration of response (DoR) (squamous NSCLC: 6.9 months vs. 4.2 months; non-squamous NSCLC: 8.6 months vs. 5.1 months). The overall survival (OS) trended towards a favorable response for the toripalimab combination (median OS of 21.0 vs. 16.0 months, HR = 0.81 [95% CI: 0.57-1.17]), but as of March 7, 2021, the data was not yet mature for a conclusion to be made. There was a controllable safety profile with no new safety concerns with the addition of toripalimab to standard chemotherapy, with 76.35% of patients experiencing a grade 3 or higher adverse event compared to 80.1% in the placebo arm. Discontinuation due to an adverse even occurred in 12.3% of patients in the toripalimab arm compared to 1.9% in the placebo arm.
With the promising results from the trial, Junshi Biosciences and Coherus will plan to meet with the US FDA for a potential biologics license application for toripalimab as first line treatment for advanced NSCLC. If the FDA grants approval it will be another ICI available on the ever-growing list for lung cancer. Currently there are at least 15 controlled studies that have been shown to reduce the risk of progression. In such a crowded space, toripalimab could potentially come out on top if it can be competitive with pembrolizumab on price.
At MEDSIR we are also exploring treatment options for lung cancer with our LUPER trial. If you want to learn more about our trials or want to collaborate on an idea with our network of investigators, contact us!
1. Wang J. CHOICE-01: a phase 3 study of toripalimab versus placebo in combination with first-line chemotherapy for advanced NSCLC. Presented at: International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer; September 8-11, 2021; Virtual. Abstract MA13.08. https://bit.ly/3iXPhWu
2. Junshi Biosciences and Coherus announce U.S. FDA breakthrough therapy designation granted for toripalimab for 1st line treatment of nasopharyngeal carcinoma. News release. Junshi Biosciences and Coherus. August 12, 2021. Accessed August 12, 2021.
3. Xu R-H, Mai H-Q, Chen Q-Y, et al. JUPITER-02: the randomized, double-blind phase 3 study of toripalimab or placebo plus cisplatin and gemcitabine as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol. 2021;39(suppl 15; abstr LBA2).