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

NCT05735080 | Recruiting Phase 1 FDA Drug

• 1 other identifier: INX-315-01
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 18

Brief 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).

Conditions

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

Keywords

CDK2; CDK4/6i; cyclin dependent kinase 2; CCNE1

Outcome Measures

Primary Outcomes (7)

• Part A and B: Evaluate the incidents of treatment emergent adverse events and laboratory abnormalities in INX-315 monotherapy and in combination with fulvestrant

  Up to 12 months

• Part A: Evaluate the occurrence of dose-limiting toxicities (DLTs) during Cycle 1

  28 days

• Part A: Recommend at least two doses of INX-315 to be evaluated in the expansion phase

  Up to 12 months

• Part B: Overall response rate (ORR)

  Up to 36 months

• Part B: Selection of Recommended Phase 2 Dose (RP2D)

  Up to 36 months

• Part C Evaluate the incidents of treatment emergent adverse events and laboratory abnormalities for patients in combination treatment (INX_315+abemaciclib+fulvestrant)

  Up to 12 months

• Part C - Evaluate the antitumor activity of INX-315 in combination with abemaciclib and fulvestrant

  Up to 12 months

Secondary Outcomes (12)

• Characterize the maximum plasma concentration (Cmax)

  Cycle 1 Day 1 and Day 15

• Characterize the time to maximum plasma concentration (Tmax)

  Cycle 1 Day 1 and Day 15

• 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

• Characterize the terminal half-life (t1/2)

  Cycle 1 Day 1 and Day 15

• Characterize the oral clearance (CL/F)

  Cycle 1 Day 1 and Day 15

Study Arms (4)

Part A: Dose Escalation

EXPERIMENTAL

Multiple doses of INX-315 monotherapy, oral administration

Drug: INX-315

Part B: Ovarian Dose Expansion

EXPERIMENTAL

INX-315 monotherapy, oral administration

Drug: INX-315

Part C: HR+/HER2- BC Dose Expansion

EXPERIMENTAL

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

Drug: INX-315; Drug: Fulvestrant; Drug: Abemaciclib

Part A INX-315 + Fulvestrant

EXPERIMENTAL

INX-315 dose plus Fulvestrant 500mg (IM)

Drug: INX-315; Drug: Fulvestrant

Interventions

INX-315 DRUG

Oral administration

Part A INX-315 + Fulvestrant; Part A: Dose Escalation; Part B: Ovarian Dose Expansion; Part C: HR+/HER2- BC Dose Expansion

Fulvestrant DRUG

Fulvestrant will be combined with INX-315

Also known as: Faslodex

Part A INX-315 + Fulvestrant; Part C: HR+/HER2- BC Dose Expansion

Abemaciclib DRUG

Abemaciclib will be combined with INX-315

Also known as: Verzenio

Part C: HR+/HER2- BC Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced unresectable or metastatic HR+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitor in the adjuvant or advanced/metastatic setting.
• Advanced/ metastatic platinum-resistant or platinum-refractory high grade serous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, with known amplification of CCNE-1 that progressed after standard systemic therapy
• 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
• 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 × 10\^9/L
• Platelet count ≥ 100 × 10\^9/L
• Estimated glomerular filtration rate (eGFR) of ≥60 mL/min
• 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
• Negative pregnancy test

You may not qualify if:

• Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.
• 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.
• Have known intracranial hemorrhage and/or bleeding diatheses.
• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
• 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.
• Resting QTcF \> 470 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
• Uncontrolled, cardiovascular disease (including hypertension) with or without medication
• 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.
• 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).
• Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
• 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).
• Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
• Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy within 2 weeks prior to study entry.
• Systemic anti-cancer therapy within 21 days or at least 5 half-lives, whichever is less, prior to the first dose of the study drug
• Prior irradiation to \> 25% of the bone marrow

Sponsors & Collaborators

• Incyclix Bio: lead

Study Sites (18)

Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Levine Cancer Institute (LCI)- Atrium Health

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke Cancer Center/ DUMC

Durham, North Carolina, 27705, United States

RECRUITING

Gabrail Cancer Research Center

Canton, Ohio, 44718, United States

RECRUITING

Next Oncology

Dallas, Texas, 75039, United States

RECRUITING

UTSW Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Oncology Consultants

Houston, Texas, 77030, United States

NOT YET RECRUITING

Next Oncology

Houston, Texas, 77054, United States

RECRUITING

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

RECRUITING

Peninsula and South Eastern Haematology & Oncology Group

Frankston, Victoria, 3199, Australia

RECRUITING

Peter MacCallum Cancer Center

Parkville, Victoria, 3052, Australia

RECRUITING

Mater Hospital

South Brisbane, 4101, Australia

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Neoplasm Metastasis

Interventions

Fulvestrant; abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Clinical Director

CONTACT

1-919-328-0003; clinicalinfo@incyclixbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A will be a dose escalation guided by BOIN design for treatment assignment and dosing rules. Part B will be a dose expansion phase, patients will be randomly assigned to receive one of the identified doses of INX-315 in monotherapy Part C will be a dose escalation followed by a dose expansion phase, patients will receive INX-315 in combination treatment with abemaciclib and fulvestrant

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: February 21, 2023
• Study Start: March 28, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be shared at the completion of the study, expected release date will be in 2028

Locations

US (15); AU (3)