BMS Submits Application for Priority Review of Opdivo plus Yervoy as First-Line Therapy for Unresectable Non-Epithelioid Malignant Pleural Mesothelioma in China

On November 23, the latest public notice on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration indicated that the combination therapy of Bristol-Myers Squibb’s (BMS) PD-1 inhibitor nivolumab and CTLA-4 antibody ipilimumab is proposed to be included in the priority review as a “drug eligible for conditional approval.” The proposed indication is for the treatment of adult patients with previously untreated, unresectable, non-epithelioid malignant pleural mesothelioma. Notably, this dual immunotherapy from BMS has previously achieved significant progress in pleural mesothelioma, holding promise to break the 15-year stalemate of no new drugs in this field.

Source: CDE Official Website

Nivolumab (Opdivo) is a PD-1 inhibitor that helps restore anti-tumor immune responses by harnessing the body’s own immune system. The drug has currently been approved globally for more than ten indications, including advanced melanoma, lung cancer, renal cell carcinoma, and Hodgkin lymphoma. In China, nivolumab was first approved for marketing in 2018, and its currently approved indications in the country include non-small cell lung cancer, head and neck squamous cell carcinoma, and gastric/gastroesophageal junction adenocarcinoma.

Ipilimumab (Yervoy) is a CTLA-4 inhibitor. As one of the primary negative regulators of T-cell responses, CTLA-4 antibodies enhance tumor-killing capacity by boosting T-cell activity. The product was approved by the U.S. FDA in 2011 for the treatment of advanced melanoma, becoming the first CTLA-4 antibody drug approved globally. In China, ipilimumab submitted a New Drug Application (NDA) at the end of 2019, and the application is currently under review and approval.

Source: CDE Official Website

The proposed indication for which the CDE has granted priority review is: nivolumab in combination with ipilimumab for the treatment of adult patients with previously untreated, unresectable, non-epithelioid malignant pleural mesothelioma. Notably, a pivotal Phase 3 clinical trial of this combination therapy in patients with previously untreated malignant pleural mesothelioma had previously met its primary endpoint of overall survival (OS).

This is a multicenter, randomized, open-label Phase 3 trial named CheckMate-743. The study enrolled a total of 605 participants, who were randomly assigned to either the experimental group or the control group. Participants in the experimental group received up to two years of treatment with nivolumab plus ipilimumab, while those in the control group received six cycles of pemetrexed plus cisplatin or carboplatin. According to the latest results presented at the Presidential Symposium of the 21st World Conference on Lung Cancer (WCLC) held online this August:

Interim analysis data showed that, compared with chemotherapy, the combination therapy extended median overall survival (OS) by 4 months (18.1 months vs. 14.1 months) and reduced the risk of death by 26%. At 24 months, 41% of patients in the experimental group remained alive (vs. 27%). Among them, the median OS for patients with epithelioid and non-epithelioid subtypes was 18.7 months (vs. 16.5 months) and 18.1 months (vs. 8.8 months), respectively.

▲Partial Results from the CheckMate-743 Study (Image Source: WCLC Official Website)

Malignant pleural mesothelioma is a highly aggressive cancer. The prognosis for patients is generally poor. Data indicate that the median overall survival for previously untreated patients with advanced or metastatic malignant pleural mesothelioma is less than one year, with a five-year survival rate of approximately 10%. Previously, various clinical treatments have yielded suboptimal outcomes.

According to a press release previously issued by Bristol-Myers Squibb (BMS), no new systemic therapies had been approved for malignant pleural mesothelioma in the past 15 years, leaving patient survival times unchanged. CheckMate-743 was the first study to demonstrate that dual immunotherapy combination treatment, compared with chemotherapy, provides significant and durable overall survival benefits as first-line therapy for patients with all histological subtypes of malignant pleural mesothelioma. Based on these data, nivolumab combined with ipilimumab is poised to become the new standard of care for this patient population.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Nov 23, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] Nivolumab Combined with Ipilimumab Significantly Prolongs Overall Survival in Patients with Malignant Pleural Mesothelioma. Retrieved April 21, 2020, from https://www.prnasia.com/story/277971-1.shtml

[3]Dual Immunotherapy Prolongs Survival While Avoiding Chemotherapy in Malignant Pleural Mesothelioma. Retrieved Aug10，2020, from https://www.iaslc.org/Dual-Immunotherapy-Prolongs-Survival-While-Avoiding-Chemotherapy-in-Malignant-Pleural-Mesothelioma

Source: Medicine Insight

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