On March 15, 2022 Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS), reported the presentation of positive results and biomarker analyses from the pivotal study "CHOICE-01" (clinicaltrials.gov identifier# NCT03856411), a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab plus chemotherapy as first-line treatment of advanced squamous or non-squamous non-small cell lung cancer ("NSCLC") (Press release, Coherus Biosciences, MAR 15, 2022, View Source [SID1234610111]). The final progression-free survival ("PFS") analysis confirms the finding of the previous interim PFS analysis, demonstrating a statistically significant and clinically meaningful improvement in PFS per RECIST v1.1 compared to chemotherapy alone. The study also demonstrated an improvement in overall survival ("OS") in a prespecified interim OS analysis. These results will be summarized later today during the ASCO (Free ASCO Whitepaper) Plenary Series, in an oral presentation by Professor Jie Wang, MD, PhD, from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. The abstract is now available on the ASCO (Free ASCO Whitepaper) website.
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"We are excited about the consistently strong clinical evidence that toripalimab has displayed across multiple tumor types," said Dr. Patricia Keegan, Chief Medical Officer at Junshi Biosciences. "The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided superior PFS and OS compared to chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as first-line therapy for advanced NSCLC patients without EGFR/ALK mutations."
"In the CHOICE-01 study in patients with non-small cell lung cancer, toripalimab has once again demonstrated the potential to delay disease progression and help patients live longer," said Theresa LaVallee, PhD, Chief Development Officer at Coherus. "The study investigators also reported interesting biomarker data with toripalimab plus chemotherapy having activity independent of PD-L1 expression as well as a statistically significant overall survival advantage in NSCLC patients who have alterations in the focal adhesion-PI3K-AKT signaling pathway, a finding which may inform the design of future toripalimab clinical trials."
About CHOICE-01
A total of 465 treatment-naïve advanced NSCLC patients without EGFR/ALK mutations were randomized (2:1): 309 to toripalimab plus chemotherapy (the "toripalimab arm") and 156 to placebo plus chemotherapy (the "placebo arm"). 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.
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 overall survival for the toripalimab arm over the placebo arm (median OS not reached vs. 17.1 months, HR = 0.69 (95% CI: 0.52-0.92)).
The PFS benefits were observed in patients treated with toripalimab plus chemotherapy across key subgroups, including histologic subtype and tumor PD-L1 expression.
Genomic analysis revealed a PFS benefit associated with high tumor mutation burden and with genetic alterations in the focal adhesion-PI3K-AKT and IL-7 pathways in patients treated with toripalimab plus chemotherapy.
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 adverse events (AEs) was 78.6% in the toripalimab arm vs. 82.1% in the placebo arm. AEs leading to discontinuation of toripalimab or placebo were 14.3% vs. 3.2%, respectively.
Junshi Biosciences and Coherus are evaluating potential registration avenues for toripalimab in combination with chemotherapy for the first-line treatment of advanced non-small cell lung cancer in the United States. In China, the supplemental New Drug Application for this indication was accepted in December 2021 by the National Medical Products Administration ("NMPA").
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 promote 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 four approved indications for toripalimab in China:
unresectable or metastatic melanoma after failure of standard systemic therapy;
recurrent or metastatic nasopharyngeal carcinoma ("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 cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC.
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 addition, two supplemental New Drug Applications ("NDAs") for toripalimab are currently under review by the National Medical Products Administration ("NMPA") in China:
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic ESCC.
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic NSCLC without EGFR or ALK mutations.
In the United States, the FDA has granted priority review for the toripalimab biologics license application ("BLA") for the treatment of recurrent or metastatic NPC, an aggressive head and neck tumor which has no FDA-approved immuno-oncology treatment options. The FDA has assigned a Prescription Drug User Fee Act ("PDUFA") target action date for April 2022 for the toripalimab BLA. The FDA granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC in 2021 as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC in 2020. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designation for the treatment of esophageal cancer, NPC, mucosal melanoma and soft tissue sarcoma. In 2021, Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple other cancer types.