On October 12, 2022 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) and Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) reported the publication of toripalimab plus chemotherapy for patients with treatment-naïve advanced non-small cell lung cancer: a multi-center randomized phase 3 trial (CHOICE-01) in the Journal of Clinical Oncology (Press release, Coherus Biosciences, OCT 12, 2022, View Source [SID1234621945]).

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Toripalimab in combination with chemotherapy was associated with significant improvements in progression-free survival (PFS) (primary endpoint) and overall survival (OS) (secondary endpoint) compared with chemotherapy alone in patients with advanced non-small cell lung cancer ("NSCLC") without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutations, regardless of PD-L1 expression. No new safety signals were observed with toripalimab in this study.

"These data support our strategy for toripalimab in non-small cell lung cancer where we plan to evaluate toripalimab in combination with other immuno-oncology agents, including our TIGIT-targeted antibody, CHS-006/JS006, in patients with NSCLC as well as for other indications in the U.S.," said Rosh Dias, MD, MRCP, Chief Medical Officer at Coherus.

A total of 465 patients with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomized 2:1 to receive toripalimab 240 mg (n=309, "the toripalimab arm") or placebo (n=156, "the placebo arm") in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo plus standard care. PFS was the primary endpoint.

Statistically significant improvements in both PFS and OS were detected in the toripalimab arm compared with the placebo arm, with similar rates of adverse events (AEs). At the final analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS 8.4 vs 5.6 months; 1-year PFS rates 36.7% vs 17.2%). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached vs 17.1 months). OS rates at 2 years were 51.2% vs 33.9%, in the two arms. The incidence of Grade > 3 AEs was similar between the two arms (78.6% vs 82.1%).

About CHOICE-01
The CHOICE-01 study was a multi-center, randomized double-blind, placebo-controlled phase 3 study conducted in 59 centers across China. 465 treatment-naïve advanced NSCLC patients without EGFR/ALK mutations were randomized to receive either toripalimab plus chemotherapy (n=309) or placebo plus chemotherapy (n=156). The primary endpoint was PFS assessed by the investigator. Secondary endpoints included PFS assessed by a blinded independent review committee (BIRC), OS, and safety. Patients from the placebo arm were actively crossed over to toripalimab treatment upon disease progression. The trial was conducted in full conformance with the ICH E6 guidelines for Good Clinical Practice and the principles of the Declaration of Helsinki.

As of October 31, 2021:

At the final analysis, a significant improvement in PFS was detected in the toripalimab arm over the placebo arm (hazard ratio (HR)=0.49; 95% confidence interval (CI): 0.39-0.61, P<0.0001) with median PFS of 8.4 vs. 5.6 months. The 1-year PFS rates for the toripalimab and placebo arms were 36.7% and 17.2%, respectively.
PFS as assessed by BIRC was also significantly longer in the toripalimab arm.
A prespecified interim analysis demonstrated a statistically significant improvement in OS for the toripalimab arm over the placebo arm (median OS not reached vs. 17.1 months, HR = 0.69 (95% CI: 0.53-0.92)).
The PFS benefits were observed in patients treated with toripalimab plus chemotherapy across key subgroups, including histologic subtype and tumor PD-L1 expression.
The addition of toripalimab to standard first-line chemotherapy in patients with advanced NSCLC showed a manageable safety profile with no new safety signals observed. The incidence of Grade ≥3 AEs was 78.6% in the toripalimab arm vs. 82.1% in the placebo arm. AEs leading to discontinuation rates of toripalimab or placebo were 14.3% vs. 3.2%, respectively.
An exploratory genomic analysis showed that high tumor mutational burden was associated with significantly better PFS in the toripalimab plus chemotherapy arm and that mutations in the FA-PI3K-Akt pathway were associated with significantly better PFS and OS in the toripalimab plus chemotherapy arm
In China, the National Medical Products Administration ("NMPA") approved the supplemental new drug application for toripalimab in combination with pemetrexed and platinum as the first-line treatment in EGRF mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous NSCLC.

About Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are six approved indications for toripalimab in China:

unresectable or metastatic melanoma after failure of standard systemic therapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic nasopharyngeal carcinoma ("NPC").
recurrent or metastatic NPC after failure of at least two 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 paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma ("ESCC");
in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous NSCLC.
The first three indications have been included in the National Reimbursement Drug List ("NRDL") (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for melanoma and NPC.

In the United States, the FDA is reviewing the Biologics License Application ("BLA") resubmission for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma ("NPC") and for toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy. The FDA has set a Prescription Drug User Fee Act ("PDUFA") action date for December 23, 2022. The FDA has granted Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer ("SCLC").

In the European Union, toripalimab was also designated as an orphan medicinal product by the European Commission for the treatment of NPC.