A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of INX-315 in Patients With Advanced Cancer
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 ER+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitor
• Advanced/ metastatic platinum-resistant or platinum-refractory epithelial ovarian cancer (including fallopian tube cancer/primary peritoneal cancer) CCNE-1 amplified tumors 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
• ECOG performance status score of 0 or 1.
• Adequate organ function as demonstrated by the following laboratory values:
‣ Hemoglobin ≥ 9.0 g/dL
⁃ Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
⁃ Platelet count ≥ 100 × 109/L
⁃ Estimated glomerular filtration rate (eGFR) of ≥60 mL/min
⁃ Part A and B: Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; ≤ 5 × ULN in the presence of liver metastases Part C: Patients with GIlbert's syndrome with a total bilirubin ≤ 2.0 × ULN and direct bilirubin within normal limits
• Negative pregnancy test