Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer
Breast Cancer
Ovarian Cancer
18 Years and older, Male and Female
INX-315-01 (primary)
NCI-2023-04176
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. 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.
Objectives
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 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 51 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 and all
study visits during the DLT assessment period, and complete the 28-day DLT period.
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 an expansion cohort, patients with ER+/HER2- breast cancer will be enrolled in
this cohort.
Eligibility
- 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) CCNE1 amplified tumors that progressed after standard systemic therapy
- Advanced or metastatic solid tumor with known amplification of CCNE1that 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
- Total bilirubin = 1.5 × ULN; AST and ALT = 2.5 × ULN; = 5 × ULN in the presence of liver metastases
- Negative pregnancy test
Treatment Sites in Georgia
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