Q702 : Axl/Mer/CSF1R Triple Inhibitor
Q702 is an orally available, selective Axl/Mer/CSF1R triple kinase inhibitor showing significant anti-tumor activities through immune activation and chemo-sensitizing effects in various tumor models.Axl and Mer receptor tyrosine kinase (RTK) have been reported as playing important roles in multiple cancer indications. Axl has been known to promote epithelial-to-mesenchymal transition (EMT) leading to drug and immune resistant tumor. Axl and Mer’s roles in inactivation of innate immunity in cancer and enveloped viral infection also have been reported. Therefore, inhibition of Axl and Mer functions has been considered as one of the good mode of actions in fighting against cancer, particularly after emergence of T cell checkpoint inhibitor therapy as Axl and Mer affects complementary innate immune system.
Colony Stimulating factor-1 receptor (CSF1R) also indicated in regulation of tumor micro-environment (TME), creating immune suppressive condition by differentiation of tumor associated macrophage (TAM) and recruitment of myeloid derived suppressor cells (MDSC). Therefore, inhibition of CSF1R functions also has been considered as effective way to activate anti-tumor immunity.
Q702 selectively inhibits Axl, Mer and CSF1R RTK at the same time, maximizing innate immune activation capacity as well as making cancer cells more drug and immune susceptible. Q702 is effective as monotherapy as well as in combination with T cell checkpoint inhibitors in various tumor models. Monotherapy activity of agents with innate immune activating mode of action has been increasingly regarded as an essential characteristic for success in clinic due to recent set-backs of leading drug candidates in the area. Q702 builds up anti-tumor immunity through multiple mode of actions, it is well positioned to be effective in severely immune suppressed conditions.
Q702 got a clearance of phase 1 study by US FDA.
Oral Axl/Mer/CSF1R Selective Tyrosine Kinase Inhibitor in Patients With Advanced Solid Tumor. (Clinical trials.gov)
Poster
1. Q701, a selective Axl/Mer inhibitor as an immune checkpoint inhibitor (2017 AACR-NCI-EORTC poster)
2. Q702, Selective Axl, Mer and CSF1R triple kinase inhibitor with dual potentials leading to tumor regression (2019 AACR annual meeting)
3. Q702, selective Axl/Mer/CSF1R triple kinase inhibitor enhance the activity of immune checkpoint inhibitor by alteration of immunosuppressive tumor microenvironment (2020 AACR poster)
4. Patient pharmacodynamic biomarker and PK evaluation results from an ongoing phase I dose-escalation study of Q702,
an Axl, Mer and CSF1R kinase inhibitor in patients with advanced solid tumors (2023 AACR poster)
5. A Phase 1, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic Study of Q702 with a Cohort Expansion at the RP2D in Patients with Advanced Solid Tumors (2023 SITC poster)
6. A Phase 1B/2, Open-label Study of Q702 in combination with intravenous Pembrolizumab in Patients with Selected Advanced Solid Tumors (2023 SITC poster)
Publications
1. A Novel Selective Axl/Mer/CSF1R Kinase Inhibitor as a Cancer Immunotherapeutic Agent Targeting Both Immune and Tumor Cells in the Tumor Microenvironment (MDPI)
Clinical Trials
1. Oral Axl/Mer/CSF1R Selective Tyrosine Kinase Inhibitor in Patients With Advanced Solid Tumor (NCT04648254)
2. Oral Axl/Mer/CSF1R Selective Tyrosine Kinase Inhibitor Q702 in Combination With Pembrolizumab in Patients With Selected Advanced Solid Tumors (NCT05438420)
Related News & publications
1. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature, 507(7493),508-12, 2014; (Mar, 27) (Pubmed)
2. Killer targets in metastasis (SciBX)
3. Qurient Announces U.S. FDA Clearance of IND Application for Q702, a Novel Cancer Immunotherapy (businesswire)
4. Qurient Enrolls First Patient in Q702 U.S. Phase 1 Study (businesswire)
5. Qurient Announces Collaboration Agreement with MSD to Evaluate Selective Triple Inhibitor Q702 in Combination With KEYTRUDA® (pembrolizumab) (businesswire)
6. Qurient Announces Dosing of First Patient in Q702 in Combination with KEYTRUDA® in a Phase 1b/2 Clinical Study for the Treatment of Patients with Solid Tumors (businesswire)