On September 13, 2021 Coherus Biosciences, Inc. (Nasdaq: CHRS) and Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) reported the presentation of positive interim results from the pivotal study "CHOICE-01" (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) without driver mutations (Press release, Coherus Biosciences, SEP 13, 2021, View Source [SID1234587656]). The interim analysis met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression free survival (PFS) per RECIST v1.1 compared to chemotherapy alone.
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The interim results were summarized on September 13 in a presentation by Professor Jie Wang, MD, PhD, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, during the Mini Oral Session at the 2021 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC). The abstract detailing the interim results was first made available on the WCLC website on August 18.
"The addition of toripalimab to standard 1st-line chemotherapy in patients with advanced non-small cell lung cancer showed superior progression free survival, overall response rate and duration of response over chemotherapy alone, with a safety profile consistent with the PD-1 inhibitor class of drugs," said Dr. Wang. "Overall survival data are still maturing, with a notable emerging trend favoring the toripalimab-chemotherapy combination. We look forward to additional data from this study and believe CHOICE-01 results will provide strong evidence to support the use of toripalimab with chemotherapy as a 1st-line therapeutic option for NSCLC."
A final analysis of progression free survival and an additional interim overall survival analysis are expected later this year. Junshi Biosciences and Coherus plan to meet with the United States Food and Drug Administration to discuss a potential submission to the pending biologics license application of an efficacy supplement for toripalimab for the first line treatment, in combination with platinum-based chemotherapy, of advanced, unresectable NSCLC without driver mutations.
"CHOICE-01 is the first of four pivotal clinical trials evaluating toripalimab for the treatment of lung cancer to have clinical data presented, and its positive results are a promising start for toripalimab in lung cancer. Lung cancer is the most common form of cancer worldwide and the leading cause of death due to cancer, so there is a clear need to develop complementary approaches to standard chemotherapy to improve patient outcomes, maintain quality of life, and seek to improve survival for patients diagnosed with this deadly disease. We will work closely with Coherus and the regulatory authorities to bring this new therapy to patients in the United States," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences.
"The CHOICE-01 interim data presented at WCLC are encouraging early evidence for toripalimab’s clinical benefit in the first-line setting in non-small cell lung cancer," said Denny Lanfear, CEO of Coherus. "We eagerly anticipate additional results from this study and the potential to advance toripalimab toward registration for this indication in the United States."
Toripalimab Phase 3 clinical trials in lung cancer
Junshi Biosciences and Coherus are currently evaluating toripalimab in four pivotal Phase 3 clinical trials in lung cancer.
CHOICE-01, with 465 patients enrolled, is comparing toripalimab in combination with chemotherapy to chemotherapy alone as first-line treatment of advanced NSCLC. The study met the primary endpoint of progression free survival (PFS) at the interim analysis (data cut-off date: November 17, 2020). Patients receiving the placebo-chemotherapy combination were allowed to actively cross over to toripalimab treatment at the time of disease progression. Overall survival (OS) data are still maturing and exhibiting a trend favoring the toripalimab-chemotherapy arm as of a March 2021 observation. Final PFS and additional interim OS analyses are expected later in 2021.
Toripalimab is also being evaluated in combination with standard platinum-based chemotherapy in patients with NSCLC harboring EGFR mutations whose tumors are no longer responding to EGFR TKI therapy. Enrollment of 350 subjects in this Phase 3 study is on track to be completed by the end of 2021. The primary endpoint of the study is PFS. Initial results are expected in 2022.
In the neoadjuvant setting, toripalimab is being evaluated in combination with chemotherapy in a Phase 3 study with 406 patients with NSCLC scheduled to undergo surgical resection of their lung cancer. Enrollment is on track to be completed by the end of 2021. The primary endpoints of the study are major pathological response and event free survival. Initial results are expected in 2022.
Toripalimab is being evaluated in combination with standard chemotherapy in a Phase 3 study with 442 patients with extensive stage small cell lung cancer. Enrollment is complete. PFS and OS are the co-primary endpoints. Results are expected by the first half of 2022.
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. Ongoing or completed pivotal clinical trials are 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 by 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 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 2021, 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 addition, two supplemental NDAs for toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic NPC or for the first-line treatment of patients with advanced, or metastatic esophageal squamous cell carcinoma were accepted by the NMPA for review in February and July 2021 respectively.
In the United States, the first toripalimab BLA has been submitted to the FDA for the treatment of recurrent or metastatic NPC. The FDA has granted Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the 1st line treatment of recurrent or metastatic NPC and for toripalimab monotherapy in the 2nd line and subsequent treatment of recurrent or metastatic NPC. There are currently no PD-1 blocking antibodies approved for use in NPC in the United States. Additionally, FDA has granted Fast Track designation for 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.