Incyclix Bio (Incyclix) is developing INX-315 as an oral, small molecule inhibitor of cyclin dependent kinase 2 (CDK2) for the treatment of human cancers. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity of INX-315 in patients with recurrent advanced/metastatic cancer, including hormone receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer who progressed on a prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) regimen, and CCNE1-amplified solid tumors who progressed on standard of care treatment. The study will be conducted in 3 parts: Part A (INX-315 monotherapy dose escalation and combination therapy with fulvestrant), Part B (ovarian cancer INX-315 monotherapy dose expansion), and Part C (INX-315 combination therapy with abemaciclib \[a CDK4/6i\] and fulvestrant \[a SERD\] in advanced/metastatic breast cancer; dose escalation and expansion).
Advanced unresectable or metastatic HR+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitor in the adjuvant or advanced/metastatic setting.
Advanced/ metastatic platinum-resistant or platinum-refractory high grade serous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, with known amplification of CCNE-1 that progressed after standard systemic therapy
Advanced or metastatic solid tumor with known amplification of CCNE-1 that has progressed after standard therapy, been intolerant to or is ineligible for standard therapy
At least one measurable lesion as defined by RECIST v1.1 that has not previously been irradiated
Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.
Have central nervous system (CNS) metastases or spinal cord compression that is associated with progressive neurological symptoms or requires corticosteroids (within 4 weeks of enrollment) to control the CNS disease.
Have known intracranial hemorrhage and/or bleeding diatheses.
Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
Sequential
INX-315
DrugOral administration
Fulvestrant
DrugFulvestrant will be combined with INX-315
Abemaciclib
DrugAbemaciclib will be combined with INX-315
Part A and B: Evaluate the incidents of treatment emergent adverse events and laboratory abnormalities in INX-315 monotherapy and in combination with fulvestrant
Part A: Evaluate the occurrence of dose-limiting toxicities (DLTs) during Cycle 1
Part A: Recommend at least two doses of INX-315 to be evaluated in the expansion phase
Part B: Overall response rate (ORR)
Characterize the maximum plasma concentration (Cmax)
Characterize the time to maximum plasma concentration (Tmax)
Characterize the Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24h)
Characterize the terminal half-life (t1/2)
Click on the lead sponsor to view all of their trials.
