Open-Label Study to Evaluate the Safety, Tolerability, PK, 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. This study will evaluate approximately 6 dose levels of daily INX-315 in Part A, at least two dose levels will be evaluated in Part B to identify the Recommended Phase 2 Dose (RP2D) in patients with ovarian cancer, and Part C will evaluate combination treatment of INX-315 plus a CDK4/6i and selective estrogen receptor degrader (SERD) in HR+/HER2- breast cancer patients who have progressed on prior CDK4/6i regimen.

Inclusion Criteria:Advanced unresectable or metastatic ER+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitorAdvanced/ metastatic platinum-resistant or platinum-refractory epithelial ovarian cancer (including fallopian tube cancer/primary peritoneal cancer) CCNE1 amplified tumors that progressed after standard systemic therapyAdvanced or metastatic solid tumor with known amplification of CCNE1that has progressed after standard therapy, been intolerant to or is ineligible for standard therapyAt least one measurable lesion as defined by RECIST v1.1 that has not previously been irradiatedECOG performance status score of 0 or 1.Adequate organ function as demonstrated by the following laboratory values:Hemoglobin ≥ 9.0 g/dLAbsolute neutrophil count (ANC) ≥ 1.5 × 109/LPlatelet count ≥ 100 × 109/LEstimated glomerular filtration rate (eGFR) of ≥60 mL/minTotal bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; ≤ 5 × ULN in the presence of liver metastasesNegative pregnancy testExclusion Criteria:Have received previous therapy with a CDK2/4/6 inhibitor, CDK2 inhibitor, PKMYT1 inhibitor, or WEE1 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.Have clinically active ongoing interstitial lung disease (ILD) of any etiology, including drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment.Resting QTcF > 470 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.Uncontrolled, cardiovascular disease (including hypertension) with or without medicationHistory of other malignancies, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated a) in situ carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively treated solid tumor with no evidence of disease for ≥ 3 years.Known HIV infection, including AIDS-related illness, or have active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus, hepatitis C virus, or COVID-19 infection (symptoms and a positive test result).Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.Have planned or anticipation of the need for major surgical procedure within 28 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy within 2 weeks prior to study entry.Systemic anti-cancer therapy within 28 days or at least 5 half-lives, whichever is less, prior to the first dose of the study drugPrior irradiation to >25% of the bone marrowPrevious high-dose chemotherapy requiring prior stem cell transplantParticipation in other studies involving investigational drug(s) within 4 weeks prior to study entry.Known or suspected hypersensitivity to active ingredient/excipients in INX-315.Known difficulty in swallowing or tolerating oral medications, or conditions which would impair absorption of oral medications