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A Study to Assess AXN-2510 Treatment in Adult Patients With Advanced Solid Tumors

Not Applicable
Recruiting
Conditions
Solid Tumor, Adult
Interventions
Biological: AXN-2510
Registration Number
NCT07159828
Lead Sponsor
Instil Bio
Brief Summary

The goal of this clinical trial is to learn more about the side effects and best dose of AXN-2510 in adults with advanced solid tumors. The main questions it aims to answer are:

* What are the side effects of AXN-2510?

* Which is the best tolerated dose of AXN-2510?

* How long does AXN-2510 stay in your body?

Participants will receive AXN-2510 every 3 weeks. Participants will visit the clinic for checkups and tests several days during the first and third doses, and once every 3 weeks for other doses.

Detailed Description

This is a phase 1 study where all adult participants will receive AXN-2510. There will be 2 increasing doses of AXN-2510 given to participants, the dose given depends on when a participant enters the study. Next will be enrollment of 20 participants at the different doses to obtain more information about side effects, tolerability, and if the drug is helping.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
52
Inclusion Criteria
  • Confirmed diagnosis of an advanced or metastatic solid tumor that is relapsed or refractory following previous therapy, and for which there is no available standard therapy.
  • Availability of PD-L1 Tumor Proportion Score (TPS) or Combined Positive Score (CPS); OR willingness to submit tumor tissue, if available, for central testing.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Age ≥ 18 years at the time of signing the informed consent.
  • Adequate hepatic function.
  • Adequate renal function.
  • Adequate bone marrow function.
  • Adequate blood clotting function
Exclusion Criteria
  • Active, untreated brain metastases or leptomeningeal disease requiring immediate local therapy, with some exceptions.
  • Concurrent malignancy that is progressing or requires active treatment, with some exceptions.
  • Received prior treatment within 5 half-lives or 4 weeks prior to starting AXN-2510, whichever is shorter (6 weeks for nitrosourea or mitomycin-C). Patients with prostate or breast cancer may continue concurrent hormone therapy.
  • Current use of immune-suppressive medication at the time of study enrollment, with some exceptions.
  • Uncontrolled hypertension defined as blood pressure of ≥ 160 mmHg systolic and/or ≥ 95 mmHg diastolic.
  • Active or clinically significant bleeding within 6 months for major bleeding or within 4 weeks for minor bleeding prior to Screening.
  • History of stroke, transient ischemic attack, or clinically significant thromboembolic event within 6 months prior to enrollment.
  • Radiographic evidence of tumor invasion into major blood vessels (e.g., pulmonary artery, carotid artery) or tumors with central necrosis or cavitation.
  • Impaired cardiac function or significant diseases.
  • History of pulmonary fibrosis or interstitial pneumonia, pneumoconiosis, chemical pneumonia, interstitial lung disease requiring steroids, or other diseases causing severe impairment of lung function.
  • Unresolved toxicity higher than Grade 1 CTCAE v5 (or most current version) attributed to any prior therapy or procedure at Screening, with exceptions for alopecia or Grade 2 neuropathy.
  • Any prior Grade 4 immune-mediated adverse event (imAE) or Grade 3 imAE requiring steroid treatment while receiving immunotherapy that has been documented within the 12 months prior to the enrollment period.
  • Known human immunodeficiency virus (HIV) or acquired immune deficiency syndromes. Note: well-controlled HIV will be allowed.
  • Positive hepatitis B surface antigen and/or hepatitis B core antibody (participants with negative polymerase chain reaction assay are permitted with appropriate antiviral therapy).
  • Active hepatitis C infection with positive viral loads. Participants who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of ≥ 12 weeks.
  • Known history of any grade hypersensitivity reactions (despite appropriate premedication) to any known components of AXN-2510 or required premedication.
  • Women who are pregnant or lactating.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that in the opinion of the investigator, might confound the results of the trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AXN-2510AXN-2510AXN-2510 given as intravenous (IV) infusion every 3 weeks, for a maximum of 24 months of treatment or until discontinuation criteria is met. Two increasing dose levels will be tested.
Primary Outcome Measures
NameTimeMethod
Incidence of Dose-Limiting Toxicities (DLTs)The first cycle of treatment (Cycle 1, Days 1-21)

A DLT is defined as a toxicity occurring during the DLT observation period

Incidence of adverse events (AEs) and serious adverse events (SAEs)From the informed consent until Day 30 post-last dose.

AEs are defined and graded according to the NCI CTCAE version 5.0

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic (PK) measure: maximum observed serum concentration (Cmax)Measured from pre-infusion Cycle 1 to Day 30 post last dose.

Measure the maximum serum concentration of AXN-2510

Changes in Pharmacodynamic (PD) biomarker T-cellsMeasured from pre-infusion Cycle 1 to Day 30 post last dose.

Changes in T-cell subtypes will be assessed

To evaluate the immunogenicity of AXN-2510.Measured from pre-infusion Cycle 1 to Day 30 post last dose.

Measure the amount of participant antibodies created against AXN-2510.

Identify if AXN-2510 is helping patients.Measured every 6 weeks for 48 weeks and every 12 weeks thereafter from first dose until disease progression or completion of the study (approximately 2 years)

Use Investigator tumor measurements to identify objective response rate, duration of response, disease control rate, time to response, and progression free survival.

Pharmacokinetic (PK) measure: area under the concentration-time curve over the dosing interval (AUCtau)Measured from pre-infusion Cycle 1 to Day 30 post last dose.

Measure the AXN-2510 concentration in blood as a function of time

Pharmacokinetic (PK) measure: minimum observed serum concentration (Cmin)Measured from pre-infusion Cycle 1 to Day 30 post last dose.

Measure the minimum serum concentration of AXN-2510

Changes in Pharmacodynamic (PD) biomarker sVEGF-AMeasured from pre-infusion Cycle 1 to Day 30 post last dose.

Activity of free soluble vascular endothelial growth factor A (sVEGF-A) will be assessed

Pharmacokinetic (PK) measure: time at which maximum serum concentration occurs (Tmax)Measured from pre-infusion Cycle 1 to Day 30 post last dose.

Measure of time to reach maximum plasma concentration after administration of AXN-2510

Trial Locations

Locations (6)

Carolina BioOncology

🇺🇸

Huntersville, North Carolina, United States

NEXT Houston

🇺🇸

Houston, Texas, United States

NEXT San Antonio

🇺🇸

San Antonio, Texas, United States

New Experimental Therapeutics (NEXT) Oncology - Houston

🇺🇸

Houston, Texas, United States

New Experimental Therapeutics of San Antonio - NEXT Oncology

🇺🇸

San Antonio, Texas, United States

NEXT Virginia

🇺🇸

Fairfax, Virginia, United States

Carolina BioOncology
🇺🇸Huntersville, North Carolina, United States

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