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

Breast Cancer Clinical Trial

— INX-315-01  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05735080
• Other study ID #: INX-315-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 28, 2023
• Est. completion date: June 2026

Study information

• Verified date: May 2024
• Source: Incyclix Bio
• Contact: Clinical Director
• Phone: 1-919-328-0003
• Email: clinicalinfo[@]incyclixbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) CCNE1 amplified tumors that progressed after standard systemic therapy

3. Advanced or metastatic solid tumor with known amplification of CCNE1that 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. Total bilirubin = 1.5 × ULN; AST and ALT = 2.5 × ULN; = 5 × ULN in the presence of liver metastases

7. Negative pregnancy test

Exclusion Criteria:

1. Have received previous therapy with a CDK2/4/6 inhibitor, CDK2 inhibitor, PKMYT1 inhibitor, or WEE1 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.

19. Known difficulty in swallowing or tolerating oral medications, or conditions which would impair absorption of oral medications

Related Conditions & MeSH terms

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

Intervention

Drug:
• INX-315
Oral administration

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Center	Parkville	Victoria
Australia	Mater Hospital	South Brisbane
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Gabrail Cancer Research Center	Canton	Ohio
United States	Levine Cancer Institute (LCI)- Atrium Health	Charlotte	North Carolina
United States	Duke Cancer Center/ DUMC	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Incyclix Bio

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A and B: Evaluate the incidents of treatment emergent adverse events and laboratory abnormalities		Up to 12 months
Primary	Part A: Evaluate the occurrence of dose-limiting toxicities (DLTs) during Cycle 1		28 days
Primary	Part A: Recommend at least two doses of INX-315 to be evaluated in the expansion phase		Up to 12 months
Primary	Part B: Overall response rate (ORR)		Up to 36 months
Primary	Part B: Selection of Recommended Phase 2 Dose (RP2D)		Up to 36 months
Secondary	Part A and B: Characterize the maximum plasma concentration (Cmax)		Cycle 1 Day 1 and Day 15
Secondary	Part A and B: Characterize the time to maximum plasma concentration (Tmax)		Cycle 1 Day 1 and Day 15
Secondary	Part A and B: Characterize the Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24h)		Cycle 1 Day 1 and Day 15
Secondary	Part A and B: Characterize the terminal half-life (t1/2)		Cycle 1 Day 1 and Day 15
Secondary	Part A and B: Characterize the oral clearance (CL/F)		Cycle 1 Day 1 and Day 15
Secondary	Part A: Overall response rate (ORR)		Up to 36 months
Secondary	Part A and B: Disease control rate (DCR)		Up to 36 months
Secondary	Part A and B: Progression free survival (PFS)		Up to 36 months
Secondary	Part A and B: Duration of response (DOR)		Up to 36 months
Secondary	Part A and B: Time to progression (TTP)		Up to 36 months
Secondary	Part A and B: Overall survival (OS)		Up to 36 months