Clinical Cancer Research Highlights Potent Antitumor Activity of Repotrectinib in Treatment-Naïve and Solvent-Front Mutation Ros1-Positive Non-Small Cell Lung Cancer

Repotrectinib Demonstrated Potent Antitumor Activity in Intracranial Preclinical Tumor Model

SAN DIEGO, April 16, 2020 (GLOBE NEWSWIRE) -- Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, today announced the publication of preclinical data and patient case studies from the Phase 1 portion of its TRIDENT-1 clinical study for its lead investigational drug, repotrectinib.

Among the findings published in the American Association of Cancer Research peer-reviewed journal, Clinical Cancer Research, repotrectinib demonstrated potent in vitro and in vivo activity in patient-derived preclinical models compared with proxy chemical compounds for other tyrosine kinase inhibitors (TKIs) against ROS1 and the ROS1 G2032R solvent-front mutation. The central nervous system (CNS) activity of repotrectinib was studied in an in vivo model and demonstrated significant reduction of metastatic brain lesions with longer survival compared to a proxy chemical compound for entrectinib.

“Our findings provide encouraging support for repotrectinib as a potential first-line treatment in ROS1-positive non-small cell lung cancer, and later-line use after progression from a prior ROS1 TKI,” said Dr. Byoung Chul Cho, Division of Medical Oncology, Yonsei Cancer Center at Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea and corresponding author of the paper. “In addition, these preclinical data as presented initially at the annual AACR conference in 2019 and now expanded upon in the publication suggest repotrectinib may prevent or delay the emergence of the G2032R solvent-front mutation and subsequent compound mutations, potentially improving clinical outcomes.”

In preclinical studies, repotrectinib potently inhibited in vitro and in vivo tumor growth and ROS1-downstream signaling in treatment-naïve models compared with proxy chemical compounds for crizotinib, ceritinib, and entrectinib. Compared to a lorlatinib proxy chemical compound in a xenograft model, repotrectinib markedly delayed the onset of tumor recurrence following drug withdrawal. In addition, repotrectinib induced anti-tumor activity in the CNS. Repotrectinib also showed selective and potent in vitro and in vivo activity against the ROS1 G2032R solvent-front mutation.