Turning Point Therapeutics Announces New Preclinical Data for Three Drug Candidates
For lead drug candidate, repotrectinib, poster presentations will highlight new preclinical combination data with MEK and MEK/Raf inhibitors, as well as repotrectinib’s potency against wildtype and mutant TRKA/B/C as compared to approved TRK inhibitors. The preclinical studies found that repotrectinib combinations with approved MEK inhibitor, trametinib, or investigational MEK/Raf inhibitor, VS-6766, were more effective than single-agent treatment in patient-derived KRAS mutant G12D/V lung and G12D/V/R pancreatic cancer models. Based on the findings and additional preclinical support presented previously, Turning Point anticipates the first cohort of its planned Phase 1/2 TRIDENT-2 study will examine the safety, tolerability, pharmacokinetics, and any early signals of efficacy of repotrectinib in combination with trametinib in patients with KRAS mutant G12D advanced solid tumors.
“We are encouraged by the new preclinical data our research team has generated in support of our ongoing development of repotrectinib, TPX-0022 and TPX-0131,” said
“In addition, preclinical studies show repotrectinib is highly potent against wild type TRK fusions and is less affected by NTRK resistance mutations than approved therapies, with strong potency in both in vitro and in vivo studies. We look forward to sharing additional clinical data from our TRIDENT-1 study of repotrectinib in the second half of the year.”
TPX-0022, MET, SRC, CSF1R Inhibitor
For MET/SRC/CSF1R inhibitor TPX-0022, the company will present preclinical data demonstrating potential utility in combination with immune checkpoint inhibitors. In a syngeneic xenograft tumor model, TPX-0022 treatment downregulated immunosuppressive cytokines, increased anti-tumor M1 macrophages, and enriched levels of CD8+ cytotoxic T cells. TPX-0022 had single agent in vivo efficacy and enhanced the efficacy of an anti-PD-1 inhibitor. With the new data, Turning Point is evaluating a potential additional combination study of TPX-0022 and an anti-PD-1 checkpoint inhibitor. In the second half of 2021, the company plans to provide a clinical data update from the Phase 1 dose finding portion of its ongoing SHIELD-1 study and initiate its planned Phase 1b/2 SHIELD-2 clinical study of TPX-0022 in combination with an EGFR targeted therapy.
TPX-0131, ALK Inhibitor
For its ALK-inhibitor, TPX-0131, Turning Point will present preclinical data showing its potential to cross the blood-brain barrier and its potency against wild type ALK and a broad spectrum of acquired ALK resistance mutations, including the G1202R solvent front mutation, L1196M gatekeeper mutation, and the G1202R/L1196M and /L1198F compound mutations. Turning Point plans to initiate a Phase 1/2 study in patients with ALK-positive TKI-pretreated advanced non-small cell lung cancer in the second quarter of 2021.
AACR plans to make poster presentations available via its website on
Title: Repotrectinib increases effectiveness of MEK inhibitors in KRAS mutant cancer models
Abstract Number: 1104
Title: Molecular characteristics of repotrectinib that enable potent inhibition of TRK fusion proteins and broad mutant selectivity
Abstract Number: 1119
Title: TPX-0022, a potent MET/SRC/CSF1R inhibitor that modulates the tumor immune microenvironment in preclinical models
Abstract Number: 1444
Title: TPX-0131, a potent inhibitor of wild type ALK and a broad spectrum of both single and compound ALK resistance mutations
Abstract Number: 1469
Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of internally discovered investigational drugs designed to address key limitations of existing cancer therapies. The company’s lead drug candidate, repotrectinib, is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors. Repotrectinib, which is being studied in a registrational Phase 2 study in adults and a Phase 1/2 study in pediatric patients, has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. The company’s pipeline of drug candidates also includes TPX-0022, targeting MET, CSF1R and SRC, which is being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in MET; TPX-0046, targeting RET, which is being studied in a Phase 1/2 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in RET; and TPX-0131, a next-generation ALK inhibitor. Turning Point’s next-generation kinase inhibitors are designed to bind to their targets with greater precision and affinity than existing therapies, with a novel, compact structure that has demonstrated an ability to potentially overcome treatment resistance common with other kinase inhibitors. The company is driven to develop therapies that mark a turning point for patients in their cancer treatment. For more information, visit www.tptherapeutics.com.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of Turning Point Therapeutics’ drug candidates, the results, conduct, progress and timing of Turning Point Therapeutics’ pre-clinical studies and plans regarding future development activities. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans”, “will”, “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Turning Point Therapeutics’ current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Turning Point Therapeutics’ business in general, risks and uncertainties related to the impact of the COVID-19 pandemic to Turning Point’s business and the other risks described in Turning Point Therapeutics’ filings with the
Source: Turning Point Therapeutics, Inc.