RECRUITING

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

Conditions

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 CDK2 CDK4/6i cyclin dependent kinase 2 CCNE1

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

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

Quick Facts

Study Start:2023-03-28

Study Completion:2026-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05735080

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	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)

Inclusion Criteria

Exclusion 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

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)

Contacts and Locations

Study Contact

Clinical Director

CONTACT

1-919-328-0003

clinicalinfo@incyclixbio.com

Study Locations (Sites)

Emory Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

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

UTSW Medical Center

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: Incyclix Bio

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-28

Study Completion Date2026-06

Study Record Updates

Study Start Date2023-03-28

Study Completion Date2026-06

Terms related to this study

Keywords Provided by Researchers

CDK2
CDK4/6i
cyclin dependent kinase 2
CCNE1

Additional Relevant MeSH Terms

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