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Official Title
A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of INX-315 in Patients With Advanced Cancer
Phase
Phase 1/Phase 2
Sponsor
Incyclix Bio
Enrollment
150
Timeline
Mar 2023 → Jun 2026
About This Study
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).
Eligibility Criteria
Inclusion Criteria
- 1Advanced unresectable or metastatic ER+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitor
- 2Advanced/ 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
- 3Advanced 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
- 4At least one measurable lesion as defined by RECIST v1.1 that has not previously been irradiated
- 5ECOG performance status score of 0 or 1.
- 6Adequate organ function as demonstrated by the following laboratory values:
- 7Hemoglobin ≥ 9.0 g/dL
- 8Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- 9Platelet count ≥ 100 × 109/L
- 10Estimated glomerular filtration rate (eGFR) of ≥60 mL/min
- 11Part 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
- 12Negative pregnancy test
Exclusion Criteria
- 1Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.
- 2Have 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.
- 3Have known intracranial hemorrhage and/or bleeding diatheses.
- 4Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
- 5Have 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.
- 6Resting QTcF \> 470 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
- 7Uncontrolled, cardiovascular disease (including hypertension) with or without medication
- 8History 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.
- 9Known 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).
- 10Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
- 11Have 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).
- 12Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
- 13Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy within 2 weeks prior to study entry.
- 14Systemic anti-cancer therapy within 28 days or at least 5 half-lives, whichever is less, prior to the first dose of the study drug
- 15Prior irradiation to \> 25% of the bone marrow
- 16Previous high-dose chemotherapy requiring prior stem cell transplant
- 17Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry.
- 18Known or suspected hypersensitivity to active ingredient/excipients in INX-315 or fulvestrant or abemaciclib.
- 19Known difficulty in swallowing or tolerating oral medications, or conditions which would impair absorption of oral medications such as active inflammatory gastrointestinal disease, uncontrolled nausea or vomiting (i.e., CTCAE ≥ Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder/active inflammation, malabsorption syndrome, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
- 20Has a serious and/or uncontrolled pre-existing medical condition(s) that, in the judgment of the Investigator or the Sponsor, would preclude participation in this study (for example but not limited to, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
Locations
17 sites participating in this study
Emory Winship Cancer Institute
Atlanta, Georgia 30322
Kevin M Kalinsky, MD
Florida Cancer Specialists
Lake Mary, Florida 32746
Alexander Philipovskiy, MD
Georgia Cancer Center at Augusta University
Augusta, Georgia 30912
Donna Wheatley
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →