NMPA Approves Kelun-Biotech's Sac-TMT for EGFRm NSCLC

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., based in CHENGDU, China, has made a significant breakthrough with the approval of its trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate, sacituzumab tirumotecan (sac-TMT). The National Medical Products Administration (NMPA) has endorsed sac-TMT for a second indication, specifically for adult patients suffering from epidermal growth factor receptor (EGFR) mutant-positive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) after the progression from EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy. This approval marks a global first for a TROP2 ADC drug targeting lung cancer and promises extended overall survival for patients compared to existing treatments.

The green light from the NMPA stems from an extensive multi-center, randomized, controlled pivotal study known as OptiTROP-Lung03. This trial assessed the efficacy and safety of sac-TMT administered as a monotherapy at a dose of 5mg/kg biweekly through intravenous injection, compared to the chemotherapy drug docetaxel. The study involved patients with locally advanced or metastatic EGFR-mutant NSCLC who had not responded to prior EGFR-TKI and platinum-based chemotherapy. Interim analysis from the study revealed that sac-TMT significantly improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared to docetaxel, demonstrating both statistical significance and clinical relevance.

Sac-TMT stands out as the first ADC to show improved overall survival benefits for patients with EGFR-mutant NSCLC after the failure of conventional treatment regimens. Previously, the NMPA had approved sac-TMT for treating adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) after they had undergone at least two systemic therapies. Additionally, a supplemental new drug application (sNDA) for sac-TMT monotherapy in EGFR-mutant NSCLC patients has been accepted.

The clinical development of sac-TMT is in full swing, with Kelun-Biotech and Merck Sharp & Dohme conducting ten registrational Phase III studies in NSCLC globally and in China. These trials explore both monotherapy and combination therapies, ranging from late-stage treatments to early postoperative adjuvant care. Among these, a notable Phase III study is underway in China, investigating sac-TMT in combination with osimertinib as a first-line treatment for locally advanced or metastatic NSCLC with EGFR mutations, titled OptiTROP-Lung07.

Dr. Michael Ge, CEO of Kelun-Biotech, expressed satisfaction with the approval of sac-TMT’s second indication, highlighting its potential to address unmet medical needs for patients with advanced EGFRm NSCLC in China. He emphasized the company’s dedication to innovation and collaboration, particularly in the area of ADCs, and looked forward to continuing research in partnership with MSD.

Lung cancer, the world's second most prevalent cancer, comprises mainly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for a significant majority. In China, the molecular profile of NSCLC differs from Western populations, with EGFR mutations present in 40 to 50% of lung adenocarcinoma cases. Current Chinese guidelines recommend EGFR-TKIs as the first treatment choice for stage IV EGFR-mutant NSCLC, but resistance necessitates new therapeutic approaches.

Sac-TMT is a pivotal product for Kelun-Biotech, featuring proprietary intellectual property and designed to target various advanced solid tumors. Developed using an innovative linker to attach a belotecan-derivative topoisomerase I inhibitor, sac-TMT works by recognizing TROP2 on tumor cell surfaces and inducing cell death through DNA damage when endocytosed. The drug also exerts a bystander effect, impacting adjacent tumor cells.

In May 2022, Kelun-Biotech granted exclusive rights to MSD, the trade name of Merck & Co., Inc., for the development and commercialization of sac-TMT outside Greater China, which includes Mainland China, Hong Kong, Macau, and Taiwan.

Kelun-Biotech, a subsidiary of Kelun Pharmaceutical, focuses on innovative drug development for addressing major health concerns such as solid tumors and metabolic diseases. The company is advancing over 30 key innovative drug projects, with a robust pipeline in various stages of clinical development, and aims to establish a global presence in the field of innovative pharmaceuticals.