Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer
Start Date
3/28/2023
Completion Date
9/1/2027
Summary
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).
Detailed Description
Study INX-315-01 is a first-in-human, Phase 1/2, open-label, dose escalation and dose-expansion study to evaluate the safety, PK, and preliminary antitumor activity of INX-315 in patients with advanced/metastatic cancers. The study will be conducted in 3 parts: Part A (dose escalation and combination therapy) and Part B (ovarian cancer dose expansion) and Part C (breast cancer dose escalation lead-in and expansion). Part A is the dose-escalation portion of the study to evaluate the safety, tolerability, and PK of INX-315 monotherapy. Dosing decisions will be guided using a Bayesian optimal interval (BOIN) design. Up to 60 patients with recurrent advanced/metastatic cancer, including patients with HR+/HER2- breast cancer who progressed on a prior CDK4/6i regimen, and solid tumors, including ovarian cancer with known amplification of CCNE1 are planned to be enrolled in Part A. Dose-limiting toxicities (DLTs) will be assessed during the first treatment cycle, i.e., the first 28 days of treatment (the DLT period). Patients who are evaluable for DLT assessment are those patients who are enrolled, received \>=80% of the planned study drug doses during the DLT assessment period, and complete the 28-day DLT period. Additionally, Part A will have two cohorts that will include INX-315 plus fulvestrant in HR+/HER2- patients who have have had prior treatment with CDK4/6i. Part B will expand at least two dose levels determined by the SMC. Part B will enroll patients with platinum-refractory or platinum-resistant advanced/ metastatic ovarian cancer patients with CCNE1 amplifications. Part B will open for enrollment once the SMC has selected the dose levels to be evaluated from the Part A portion of the study. Part A patients cannot re-join or continue the study in Part B. Approximately 30 patients will be equally randomized to receive one of the dose levels of INX-315. Part C will be a dose escalation and expansion cohort, patients with HR+/HER2- breast cancer will be enrolled in this cohort. Patients will receive INX-315 along with abemaciclib and fulvestrant. Approximately 50 patients will be enrolled in Part C.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
INX-315
Fulvestrant
Abemaciclib
Conditions
Locations
Florida Cancer Specialists
Orlando, Florida 32827
United States
Emory Winship Cancer Institute
Atlanta, Georgia 30322
United States
Georgia Cancer Center at Augusta University
Augusta, Georgia 30912
United States
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana 46804
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Levine Cancer Institute (LCI)- Atrium Health
Charlotte, North Carolina 28204
United States
Duke Cancer Center/ DUMC
Durham, North Carolina 27705
United States
Gabrail Cancer Research Center
Canton, Ohio 44718
United States
Next Oncology
Dallas, Texas 75039
United States
UTSW Medical Center
Dallas, Texas 75390
United States
Oncology Consultants
Houston, Texas 77030
United States
Next Oncology
Houston, Texas 77054
United States
Northwest Medical Specialties, PLLC
Tacoma, Washington 98405
United States
Peninsula and South Eastern Haematology & Oncology Group
Frankston, Victoria 3199
Australia
Peter MacCallum Cancer Center
Parkville, Victoria 3052
Australia
Mater Hospital
South Brisbane, 4101
Australia