The latest research report of Entrectinib

ASCO 2019, the largest, highest academic and most authoritative clinical oncology conference in the world, was held in Chicago from May 31 to June 4. At the ASCO annual meeting, a number of new drug data were released, among which the targeted drug Entrectinib brought amazing clinical data and became a star in the spotlight.

Introduction of Entrectinib

Entrectinib is a tyrosine kinase inhibitor (TKI), with central nervous system (CNS) activity. It is targeted to treat solid tumors with fusion mutations of NTRK1/2/3 (encoding TRKA/TRKB/TRKC), ROS1 and ALK genes. As an oral drug with CNS activity, it is used to treat neurotrophic promyosin receptor kinase (NTRK) fusion positive locally advanced or metastatic solid tumors in adults and pediatrics. It has been awarded breakthrough therapy by the US Food and Drug Administration (FDA), priority drug qualification by the European Drug Administration (EMA), and SAKIGAKE qualification (pioneer qualification) by the Japanese health authorities. These titles indicate that there is a huge unmet demand for NTRK fusion positive cancer patients, and the emergence of Entrectinib fills a big gap.

Clinical Data of Entrectinib

The clinical data presented at the meeting included 54 patients with NTRK fusion and 53 patients with ROS1 fusion, covering ten different types of cancer patients: sarcomas, non-small cell lung cancer, breast-like secretory carcinoma, colorectal cancer, bile duct carcinoma, other gynecological tumors, neuroendocrine carcinoma, salivary adenocarcinoma, and pancreatic cancer. Of these, 22 percent of patients with NTRK fusion had brain metastasis and 43 percent of patients with ROS1 fusion had brain metastasis.

For NTRK fusion: a total of 54 patients, objective remission rate of 57%, of which 42 patients without brain metastasis objective remission rate of 59.5%, 12 patients with brain metastasis objective remission rate of 50%.

For ROS1 fusion: a total of 53 patients, the objective remission rate was 77%, of which 30 patients without brain metastasis had an objective remission rate of 80%, 23 patients with brain metastasis had an objective remission rate of 73.9%.

The tolerance of Entrectinib was good, the common side effects were grade 1-2, the overall safety was controllable, and there were no grade 5 treatment related adverse events.

The above clinical trial results show that Entrectinib has a good effect against brain metastasis, it can cross the blood-brain barrier, deal with the existing CNS lesions and may prevent or delay the occurrence of brain metastasis. ROS1 fusion occurs in about 1% to 2% of NSCLC cases, and the CNS activity of Entrectinib is a key differential feature of the compound because of the tumor’s tendency to spread to the brain.

Other clinical trials

Entrectinib has completed two phase I clinical studies: STARTRK-1 and ALKA-372-001. Of the patients with ROS1 rearrangement in both studies, the total remission rate was 86% (12/14), of which two patients developed complete remission. 11 of the 13 patients with ROS1 rearrangement NSCLC achieved remission (85%), of which 1 patient with ROS1 gene fusion lasted for 27 months.

In a variety of tumor patients carrying NRTK rearrangement gene, the remission rate was 100% (5/5), including colorectal cancer patients with LMNA-NTRK1 rearrangement, astrocytoma patients with BCAN-NTRK1 rearrangement, infant fibrosarcomas with ETV6-NTRK3 rearrangement, NSCLC patients with SQSTM1-NTRK1 rearrangement and MASC patients with ETV6-NTRK3 rearrangement.

At the last AACR conference, the therapeutic results of Entrectinib in NTRK fusion gene positive NSCLC were reported, and the data were also very optimistic.

The study included 10 patients with advanced NTRK fusion NSCLC. The results showed that the remission rate of Entrectinib was as high as 70%, the progression-free survival time was 12 months, and the overall survival time was 20 months.


Following the launch of Larotrectinib, Entrectinib has become another promising NTRK targeting drug, which will provide more treatment options for patients with NTRK fusion gene NSCLC. In addition, studies have shown that Entrectinib has a good blood-brain barrier permeability, for NTRK fusion of brain metastasis patients, can also obtain better results. Entrectinib is bound to come to the fore in the field of individualized treatment of cancer.


1. Robinson, G. W., Gajjar, A. J., Gauvain, K. M., Basu, E. M., Macy, M. E., Maese, L. D., … & Weiss, B. D. (2019). Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors.

2. Abdulla, D. S. Y., Doebele, R. C., Ahn, M. J., Siena, S., Drilon, A., Krebs, M. G., … & Seto, T. (2019). ENCORE: Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC).Pneumologie73(S 01), P623.