On June 3, 2021 Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) reported positive results from the pivotal study "JUPITER-02", a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) (Press release, Coherus Biosciences, JUN 3, 2021, View Source [SID1234583499]). The interim analysis met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression free survival (PFS) compared to chemotherapy alone (assessed by a blinded independent review committee, or BIRC, per RECIST v1.1). JUPITER-02 also met secondary endpoints of PFS assessed by the investigator and objective response rate (ORR) assessed by BIRC. There was also a longer duration of response (DoR), a higher disease control rate (DCR) and higher one- and two-year survival rates for the toripalimab arm. The safety profile of toripalimab was consistent with that observed in previously reported toripalimab clinical trials.
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The results are summarized in a late-breaking abstract that will be presented during a plenary session at the 2021 annual meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) on Sunday, June 6, 2021 from 1–4 pm Eastern Daylight Time. The abstract (LBA2) is now available on the ASCO (Free ASCO Whitepaper) website.
"Nasopharyngeal carcinoma is an aggressive tumor—especially for patients with advanced NPC. For first line treatment, platinum-based chemotherapy remains the current standard of care, yet mPFS is only about 7 months. We are encouraged by the JUPITER-02 results showing the addition of toripalimab to chemotherapy as first-line treatment provided superior PFS and ORR and longer DoR than chemotherapy alone, and with a safety and tolerability profile consistent with the PD-1 antibody class of drugs," said Dr. Ruihua Xu, President and Professor, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou. "I believe that these results support the use of toripalimab with chemotherapy as the new standard of care for first-line treatment of patients with recurrent/metastatic NPC."
More than 30 toripalimab abstracts were accepted for ASCO (Free ASCO Whitepaper) 2021, including two selected for oral presentations (LBA2 and #9512), describing the antitumor activities observed from various cancers of the nasopharynx, skin, lung, esophagus, stomach, liver, biliary duct, head and neck, and pancreas. Importantly, ten of the abstracts demonstrated toripalimab’s potential in perioperative, adjuvant, or neoadjuvant treatment settings.
"Given the outstanding results, JUPITER-02 is the first study to show a major therapeutic advance for first-line treatment of advanced NPC since the chemotherapy combination of gemcitabine and cisplatin was established as standard of care, which is why I believe this study was selected for presentation at the plenary session at ASCO (Free ASCO Whitepaper) 2021. We will work to expedite commercialization of toripalimab for this patient population in China, the United States, and other countries to make this exciting new treatment option broadly available to all patients with NPC," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "In addition to the JUPITER-02 trial, results of multiple other studies of toripalimab will be presented during the ASCO (Free ASCO Whitepaper) annual meeting, which support the current development strategy, such as perioperative immunotherapy in patients with multiple solid tumors, including mucosal melanoma, esophageal cancer, gastric cancer, liver cancer and non-small cell lung cancer, as well as the exploration of toripalimab for treatment of ICC, for which no checkpoint inhibitors have been approved for use."
"ASCO 2021 is a pivotal moment for Coherus as it marks the U.S. medical meeting debut of the immuno-oncology franchise we are building to deliver life-changing medicines addressing both rare and highly prevalent cancers," said Denny Lanfear, CEO of Coherus. "The strong late-breaking data in advanced NPC add to the favorable efficacy and safety profile that is emerging for toripalimab in the broad development program with more than 15 pivotal clinical trials. Alongside Junshi Biosciences, we look forward to presenting clinical data from these studies and to working together to register toripalimab in the United States and Canada as a potential new therapeutic option across a broad range of tumor types, starting with NPC."
About JUPITER-02 Results
JUPITER-02, conducted in mainland China, Taiwan and Singapore, is the largest Phase 3 clinical study to evaluate a checkpoint inhibitor plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma. Two hundred eighty-nine patients with advanced NPC who had received no prior chemotherapy for recurrent/metastatic disease were randomized 1:1 to receive toripalimab 240 mg or placebo in combination with gemcitabine 1000 mg/m2 (d1, 8) and cisplatin 80 mg/m2 (d1), Q3W followed by toripalimab or placebo monotherapy until disease progression, intolerable toxicity or completion of two years of treatment. Progression-free survival and response were assessed by the BIRC and by the investigator per RECIST v1.1. There was one pre-specified interim analysis of PFS at 130 (65%) PFS events with a planned final analysis at 200 PFS events.
By May 30, 2020, the date of the interim analysis data cut, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. The ASCO (Free ASCO Whitepaper) presentation also includes an updated overall survival (OS) analysis with a data cut-off of February 18, 2021.
A summary of the results is as follows:
A significant improvement in PFS (assessed by BIRC) was observed in the toripalimab plus chemotherapy arm compared to the chemotherapy alone arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), median PFS of 11.7 vs. 8.0 months;
The 1-year PFS rates were 49% and 28%, respectively, for the toripalimab arm compared to the placebo arm;
An improvement in PFS was observed across relevant subgroups including patients with high PD-L1 expression (TC or IC ≥ 1%; mPFS 11.4 vs. 8.2 month, HR = 0.59 [95% CI: 0.388 – 0.893]) or low PD-L1 expression (TC and IC<1%; mPFS 11.0 vs. 6.0 months, HR=0.35 [95% CI: 0.153 – 0.808]);
The ORR was 77.4% vs. 66.4% (P = 0.034); the median DoR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]), P = 0.001);
The first interim analysis of overall survival was not mature at the interim analysis of PFS. In the updated OS analysis conducted February 18, 2021, although median OS was not yet mature in either arm, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.60 [95% CI: 0.364-0.997], nominal P = 0.046);
The incidence of grade ≥3 treatment emergent adverse events (TEAEs) (89.0% vs 89.5%), grade ≥3 treatment related adverse events (TRAE) (80.8% vs 83.2%), AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%), and fatal AEs (2.7% vs 2.8%) was similar between both arms. Immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab group.
A pre-specified second interim OS analysis will be performed at the same time as the final PFS analysis.
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 is thought to recharge 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, including in China and the United States. Pivotal clinical trials are ongoing or completed evaluating the safety and efficacy of toripalimab for 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). On December 17, 2018, toripalimab was granted a conditional approval from the National Medical Products Administration (NMPA) for the second-line treatment of unresectable or metastatic melanoma. In December 2020, toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021, the supplemental NDA for toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic nasopharyngeal carcinoma was accepted by the NMPA. In the same month, the NMPA granted a conditional approval to toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. In April, NMPA granted a conditional approval to toripalimab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
In the United States, a rolling submission of the first toripalimab Biologics License Application (BLA) is underway for the treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC). The U.S. Food and Drug Administration (FDA) has granted toripalimab Breakthrough Therapy Designation for this indication. There are currently no PD-1 blocking antibodies indicated for use in NPC in the United States. Additionally, FDA has granted Fast Track status for the development of toripalimab for the treatment of mucosal melanoma and orphan drug designation for NPC, mucosal melanoma and soft tissue sarcoma. Earlier 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 rare cancers and highly prevalent cancers.