Study of TBX-3400 in Patients With Stage III and IV Melanoma Resistant or Refractory to Immune Checkpoint Inhibitors

NCT03385486 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: TBX-3400-001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

This is a study of transfusion of TBX-3400 in patients with stage III and IV melanoma resistant or refractory to Immune Checkpoint Inhibitors. The patient's own blood cells are exposed to a protein that has been shown in the laboratory to result in anti-tumor activity. The study hypothesis is that TBX-3400 cells will enhance anti-tumor activity and improve the body's immune response.

Conditions

Stage III Melanoma; Stage IV Melanoma

Keywords

Melanoma; Resistant; Refractory

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of treatment-emergent adverse events (TEAEs), including the incidence of dose-limiting toxicities (DLTs), graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  Adverse events from subject reporting

  26 months

Secondary Outcomes (4)

• Tumor responses as defined by RECIST version 1.1

  26 months

• Tumor responses as defined by irRECIST

  26 months

• Assessment of concentrations of certain chemokines, such as cluster of differentiation 69 (CD69), as biomarkers of activity of TBX-3400

  26 months

• Presence and/or concentration of anti TBX-3400 antibodies

  26 months

Other Outcomes (6)

• Quantification of the concentration of interleukin-1 (IL-1) in plasma

  26 months

• Quantification of the concentration of interleukin-6 (IL-6) in plasma

  26 months

• Quantification of the concentration of interferon-alpha (INF-α) in plasma

  26 months

Study Arms (1)

TBX-3400

EXPERIMENTAL

TBX-3400 by intravenous infusion

Biological: TBX-3400

Interventions

TBX-3400 BIOLOGICAL

Autologous transfusion

TBX-3400

Eligibility Criteria

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

You may qualify if:

• Histopathologically confirmed diagnosis of advanced, unresectable or metastatic malignant melanoma
• Male or female patients age 18 or older
• Previously treated with checkpoint inhibitor therapy either alone or in combination with either stable disease or progressive disease per RECIST version 1.1 (there is no minimum treatment duration for patients who have progressive disease while on checkpoint inhibitor therapy)
• Measurable or evaluable disease by RECIST version 1.1
• Capable of understanding and complying with protocol requirements
• A life expectancy of greater than 24 weeks at Screening
• ECOG Performance Status of 0 to 2
• Written informed consent from the patient or the patient's legally acceptable representative prior to the initiation of any study procedures
• Adequate bone marrow, liver, and renal function as defined below:
• hemoglobin ≥8.0 g/dL (transfusions allowed)
• absolute neutrophil count ≥1500/µL
• platelet count ≥100,000/µL (transfusions allowed)
• alanine transaminase and aspartate transaminase ≤3.0 times the upper limit of normal (ULN), or ≤5 times ULN for patients with known hepatic metastases
• total serum bilirubin ≤1.5 x the ULN; ≤2.0 x the ULN if liver metastases are present; patients with a known history of Gilbert's syndrome (≤3.0 x the ULN) and/or isolated elevations of indirect bilirubin are eligible for study participation
• estimated glomerular filtration rate ≥50 mL/min/1.73 m\^2 (using Cockcroft Gault formula)

You may not qualify if:

• Patients who meet any of the following criteria will not be eligible for participation in the study:
• Pregnant or breast feeding
• Developed immune-related toxicity while on prior checkpoint inhibitor therapy that has not yet returned to Grade 1 or better
• Require systemic pharmacologic doses of corticosteroids at or above the equivalent of 10 mg/day of prednisone; replacement doses, topical, ophthalmologic and inhalational steroids are permitted
• Active, symptomatic central nervous system (CNS) metastases. Patients with CNS metastases are eligible for the trial if the metastases have been treated by surgery and/or radiotherapy and the patient is off corticosteroids and is neurologically stable for at least 7 days prior to screening
• Any concurrent uncontrolled illness, including mental illness or substance abuse which in the opinion of the investigator would make the patient unable to cooperate or participate in the trial
• Severe uncontrolled cardiac disease within 3 months of study entry, including unstable or new onset angina, myocardial infarction or cerebrovascular accident
• Women of childbearing potential who are unable or unwilling to use an acceptable method of contraception
• Known infection with human immunodeficiency virus (HIV) that is not well controlled on anti-retroviral therapy as defined by HIV RNA more than 400 copies/mL or severely symptomatic
• Presence of Hepatitis B and/or Hepatitis C active infection
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher

Sponsors & Collaborators

• Taiga Biotechnologies, Inc.: lead

Study Sites (2)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

RECRUITING

University of Colorado Cancer Center

Denver, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Yosef Refaeli, PhD

CONTACT

+1-720-859-3547; refaeli@taigabiotech.com

Vivienne Margolis

CONTACT

+972-52-463-9634; vmargolis@taigabiotech.com

Study Design

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

Model Details: The study will consist of a Dose Escalation Phase and a Dose Expansion Phase. TBX-3400 will be administered on Day 1 of each treatment cycle and can be repeated. In the Dose Escalation Phase, a "3+3" design will be employed. Each dose cohort will initially enroll 3 patients. Enrollment and treatment of the first 3 patients in the first cohort will be staggered to allow for evaluation of safety. After each cohort has been enrolled and all patients in the cohort have completed Cycle 1, a Data Safety Monitoring Committee will review cumulative safety data to determine whether to proceed with further dose escalation. Each cohort may be expanded in groups of 3 patients to a maximum of 12 patients. Up to six TBX 3400 dose levels will be evaluated during the Dose Escalation Phase of the study.

Study Record Dates

• First Submitted: December 3, 2017
• First Posted: December 28, 2017
• Study Start: June 2, 2019
• Primary Completion: February 1, 2023
• Study Completion: December 1, 2024
• Last Updated: May 3, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)