A Phase 1/2, Open-Label, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of INX-315 in Patients with Advanced Cancer

Cancer Categories

Breast,Gynecologic

Karmanos Trial ID

2024-097

NCT ID

NCT05735080

Age Group

Adult

Scope

National

Phase

Phase I/II

Principal Investigator

Ira
Winer, M.D., Ph.D., FACOG
Oncology - Gynecologic, Oncology - Surgical View Profile

Objective:

Part A (Dose Escalation

Primary Objectives

To determine the safety and tolerability of INX-315 monotherapy and in combination with fulvestrant.
To recommend at least two dosages of INX-315 to be evaluated in the expansion portion (Part B).

Secondary Objectives

To characterize the systemic PK profile of INX-315 monotherapy and in combination with fulvestrant
To evaluate the antitumor activity of INX-315 per RECIST v1.1 as a monotherapy and in combination with fulvestrant.

Part B (Ovarian Cancer Dose Expansion)

Primary Objectives

To confirm the safety and tolerability of INX-315 when administered at the dosages selected from Part A.
To evaluate the antitumor activity of INX-315 per RECIST v1.1.
To determine the Recommended Phase 2 Dose (RP2D) based on data from Parts A and B.

Secondary Objectives

To characterize the systemic PK profile of INX-315.
To evaluate the antitumor activity of INX-315 per RECIST v1.1 in terms of other efficacy endpoints.
Part C (Breast Cancer Combination Treatment)

Primary Objectives

To determine the safety and tolerability of INX-315 in combination with abemaciclib and fulvestrant
To evaluate the antitumor activity of INX-315 in combination with abemaciclib and fulvestrant per RECIST v1.1.

Secondary Objectives

To characterize the systemic PK profile of INX-315 and abemaciclib and active metabolites (M2 and M20) alone and in combination with INX-315.
To evaluate the antitumor activity of INX-315 in combination with abemaciclib and fulvestrant per RECIST v1.1 in terms of other efficacy endpoints.
To determine the recommended dose or doses for further study

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Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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 28 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
Previous high-dose chemotherapy requiring prior stem cell transplant
Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry.
Known or suspected hypersensitivity to active ingredient/excipients in INX-315 or fulvestrant.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices