Recently, TYK Medicines announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) has granted conditional market authorization on conducting a pivotal phase II clinical trial for TY-9591, a new drug targeting lung cancer with brain metastases.

TY-9591, an innovative, highly selective, and safe novel Epidermal Growth Factor Receptor (EGFR) inhibitor with a full intellectual patent of Category 1 chemical drug granted by CDE. A phase I study exploring safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD), a phase II study evaluating efficacy of lung cancer with brain metastases, and a study to compare the pharmacokinetics of TY-9591 with Osimertinib (TAGRISSO®) and the effect of food on the pharmacokinetics of TY-9591 were conducted since the approval of IND in October 2019. TY-9591 has demonstrated excellent efficacy and a favorable safety profile in the treatment of non-small cell lung cancer with brain metastases.

Yusheng Wu, Ph.D, Chairman/CEO of TYK Medicines said: “We are very glad to hear this news, which is  an approbation of the strength of our R&B team and greatly encourages our enthusiasm for innovation. TY-9591, independently developed by TYK Medicines, is the first innovative drug to enter the clinical stage, with high bioavailability, great permeability passing blood-brain-barrier (BBB) and few toxic metabolites, was found to be greatly effective, safe, and tolerable in completed preclinical and clinical studies. With this phase II conditional marketing authorization, the key clinical study and the path to market will be more transparent. TYK will leverage more resources on rapid initiation and accelerated completion of this registered phase II clinical study. If the expected clinical outcomes have been observed in this study, TYK will boost the pace of conditional marketing application.”

Xiugui Chen, Vice President of TYK Medicines said: “The number of new cases of lung cancer in China reached 820,000 in 2020 ^[1], regretted that the incidence of advanced NSCLC with brain metastases could reach as high as about 60%. Meanwhile, the cumulative incidence of brain metastasis boosts year by year due to the prolongation of survival. However, the average survival is only 1-2 months ^[2], indicating poor prognosis, which seriously endangers patients’ survival and life quality. There is no effective drugs for NSCLC with brain metastases has been approved worldwide, which is definitely a painful point of clinical treatment with a huge unmet clinical need. TY-9591 presented excellent clinical efficacy with an intracranial objective response rate (iORR) of 100%, a complete response (CR) of 14%, and a median depth of response of 62% in NSCLC patients with brain metastases in phase I and II studies. Common adverse events observed were abnormal laboratory tests such as reduced blood counts, the vast majority of which were grade 1-2 and generally safe is manageable. We expect that the pivotal phase II clinical study of TY-9591 for NSCLC with brain metastases will be initiated rapidly and carried out smoothly, and under close cooperation with the sites and investigators, finishing enrollment of patients as soon as possible, boosting the pace of the drug gaining approval for marketing, to bring this promising treatment for the huge-scale potential patients.”

About NSCLC with brain metastases

Non-small cell lung cancer (NSCLC) is the malignancy with the highest incidence and mortality in China, and about 20%-40% of patients will develop brain metastasis during the disease progression ^[3]. The incidence of brain metastases is higher in patients harboring the driver gene of lung cancer, and brain metastases can occur in up to 44-63% of advanced lung adenocarcinoma with EGFR mutation ^[4]. The benefit bringing by the existing standard clinical therapies is limited, with objective intracranial remission rates of approximately 23%-45% and median survival of approximately 3-6 months with radiotherapy ^[5]. With the cumulative incidence of brain metastases increasing year by year, the treatment of brain metastases from lung cancer is a bottleneck to improving long-term survival in lung cancer. Improving the quality of life and prolonging the survival time of patients with brain metastases from lung cancer are still unmet clinical needs and difficulties.

References

[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. Doi:10.3322/caac.21660.

[2] Oncologist Branch of Chinese Medical Doctor Association. Guidelines for the treatment of lung cancer brain metastases in China（2021 Edition）[J]. Chinese Journal of Oncology, 2021, 43(3):269-281.

[3] Mujoomdar A, Austin JHM, Malhotra R, et al. Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma: primary tumor size, cell type, and lymph node metastases[J]. Radiology, 2007, 242(3): 882-888.

[4] Zhao B, Wang Y, Wang Y, et al. Efficacy and safety of therapies for EGFR-mutant non-small cell lung cancer with brain metastasis: an evidence-based Bayesian network pooled study of multivariable survival analyses. Aging (Albany NY). 2020;12(14):14244-14270.

[5] Sperduto P W, Shanley R, Luo X, et al. Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Post stratified by the Graded Prognostic Assessment (GPA)[J]. International Journal of Radiation Oncology Biology Physics, 2013, 87(2): S51-S52.