Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer

NCT ID: NCT05735080

Last Updated: 2025-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-28

Study Completion Date

2026-06-30

Brief Summary

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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

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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 an 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.

Conditions

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Breast Cancer Breast Cancer Metastatic Hormone Receptor Positive Tumor Human Epidermal Growth Factor 2 Negative Carcinoma of Breast Ovarian Cancer CCNE1 Amplification Solid Tumor Advanced Cancer Metastatic Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Part A will be a dose escalation guided by BOIN design for treatment assignment and dosing rules.

Part B will be dose expansion, patients will be randomly assigned to receive one of the identified doses of INX-315 in monotherapy

Part C will be dose expansion, patients will receive INX-315 in combination treatment with abemaciclib and fulvestrant
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: Dose Escalation

Multiple doses of INX-315 monotherapy, oral administration

Group Type EXPERIMENTAL

INX-315

Intervention Type DRUG

Oral administration

Part B: Ovarian Dose Expansion

INX-315 monotherapy, oral administration

Group Type EXPERIMENTAL

INX-315

Intervention Type DRUG

Oral administration

Part C: HR+/HER2- BC Dose Expansion

INX-315 in combination with abemaciclib (oral administration) and fulvestrant (IM)

Group Type EXPERIMENTAL

INX-315

Intervention Type DRUG

Oral administration

Fulvestrant

Intervention Type DRUG

Fulvestrant will be combined with INX-315

Abemaciclib

Intervention Type DRUG

Abemaciclib will be combined with INX-315

Part A INX-315 + Fulvestrant

INX-315 dose plus Fulvestrant 500mg (IM)

Group Type EXPERIMENTAL

INX-315

Intervention Type DRUG

Oral administration

Fulvestrant

Intervention Type DRUG

Fulvestrant will be combined with INX-315

Interventions

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INX-315

Oral administration

Intervention Type DRUG

Fulvestrant

Fulvestrant will be combined with INX-315

Intervention Type DRUG

Abemaciclib

Abemaciclib will be combined with INX-315

Intervention Type DRUG

Other Intervention Names

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faslodex Verzenio

Eligibility Criteria

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Inclusion Criteria

1. Advanced unresectable or metastatic ER+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitor
2. 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
3. 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
4. At least one measurable lesion as defined by RECIST v1.1 that has not previously been irradiated
5. ECOG performance status score of 0 or 1.
6. Adequate organ function as demonstrated by the following laboratory values:

1. Hemoglobin ≥ 9.0 g/dL
2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
3. Platelet count ≥ 100 × 109/L
4. Estimated glomerular filtration rate (eGFR) of ≥60 mL/min
5. 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
7. Negative pregnancy test

Exclusion Criteria

1. Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.
2. 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.
3. Have known intracranial hemorrhage and/or bleeding diatheses.
4. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
5. 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.
6. Resting QTcF \> 470 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
7. Uncontrolled, cardiovascular disease (including hypertension) with or without medication
8. History 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.
9. 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).
10. Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
11. 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).
12. Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
13. Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy within 2 weeks prior to study entry.
14. Systemic anti-cancer therapy within 28 days or at least 5 half-lives, whichever is less, prior to the first dose of the study drug
15. Prior irradiation to \> 25% of the bone marrow
16. Previous high-dose chemotherapy requiring prior stem cell transplant
17. Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry.
18. Known or suspected hypersensitivity to active ingredient/excipients in INX-315 or fulvestrant or abemaciclib.
19. Known 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.
20. Has 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyclix Bio

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Florida Cancer Specialists

Lake Mary, Florida, United States

Site Status RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, United States

Site Status RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Site Status RECRUITING

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Levine Cancer Institute (LCI)- Atrium Health

Charlotte, North Carolina, United States

Site Status RECRUITING

Duke Cancer Center/ DUMC

Durham, North Carolina, United States

Site Status RECRUITING

Gabrail Cancer Research Center

Canton, Ohio, United States

Site Status RECRUITING

Next Oncology

Dallas, Texas, United States

Site Status RECRUITING

UTSW Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Oncology Consultants

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

Next Oncology

Houston, Texas, United States

Site Status RECRUITING

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

Site Status RECRUITING

Peter MacCallum Cancer Center

Parkville, Victoria, Australia

Site Status RECRUITING

Mater Hospital

South Brisbane, , Australia

Site Status RECRUITING

Countries

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United States Australia

Central Contacts

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Clinical Director

Role: CONTACT

1-919-328-0003

Facility Contacts

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Aimee Jackson

Role: primary

Donna Wheatley

Role: primary

Andrea Vasquez

Role: primary

Meghan Levesque

Role: primary

Madeline McGinnis

Role: primary

313-576-9380

Ask Roswell

Role: primary

800-767-9355

Carrie Smith, RN

Role: primary

Fope Akinwale

Role: primary

Isabel Valenciana

Role: primary

Site PI

Role: primary

713-600-0913

Fope Akinwale

Role: primary

Sue Quinsey

Role: primary

253-428-8700

Kim Nayeon

Role: primary

Other Identifiers

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INX-315-01

Identifier Type: -

Identifier Source: org_study_id

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