Study of TBX-3400 in Subjects With Solid Malignant Tumors Resistant or Refractory to Standard Therapies

• ClinicalTrials.gov Identifier: NCT04640246
• Recruitment Status: Recruiting
• First Posted: November 23, 2020
• Last Update Posted: February 2, 2022
• Sponsor: Taiga Biotechnologies, Inc.
• Information provided by (Responsible Party): Taiga Biotechnologies, Inc.

Study Description

Brief Summary:

This is a study of treatment with TBX-3400 in subjects with solid malignant tumors that are resistant or refractory to standard therapies.

The subject'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 to the tumor.

Condition or disease	Intervention/treatment	Phase
Cancer; Tumor, Solid; Refractory Cancer	Biological: TBX-3400	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Multi-Center Dose-Escalation Study of the Safety, Tolerability and Early Efficacy of TBX-3400 in Subjects With Solid Malignant Tumors Resistant or Refractory to Standard Therapies
• Actual Study Start Date: January 25, 2021
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: TBX-3400; TBX-3400 by intravenous infusion	Biological: TBX-3400; Autologous transfusion

Outcome Measures

Primary Outcome Measures :

1. The primary endpoint is the 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 5.0. [ Time Frame: 8 months ]
   Adverse events from subject reporting

Secondary Outcome Measures :

1. Tumor Responses as defined by RECIST [ Time Frame: 8 months ]
   Tumor measurements to assess disease state
2. Assessment of concentrations of certain proteins such as cluster of differentiation 69 (CD69), as biomarkers of activity of TBX-3400 [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400
3. Presence and/or concentration of anti TBX-3400 antibodies [ Time Frame: 8 months ]
   Measure of immunogenicity of TBX-3400

Other Outcome Measures:

1. Quantification of the concentration of interleukin-1 (IL-1) in plasma [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400
2. Quantification of the concentration of interleukin-6 (IL-6) in plasma [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400
3. Quantification of the concentration of interferon-alpha (IFN-α) in plasma [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400
4. Quantification of the concentration of interferon-gamma inducible protein 10kD (IP-10) in plasma [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400
5. Quantification of the concentration of interferon-gamma (IFN-γ) in plasma [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400
6. Quantification of the concentration of transforming growth factor-beta (TGF-ß) in plasma [ Time Frame: 8 months ]
   Preliminary efficacy assessment to measure activity of TBX-3400

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation in the study:

1. Histologically or cytologically confirmed diagnosis of malignant solid tumor/s
2. Male or female subjects age 18 or older
3. Metastatic tumor that has failed at least one line of therapy with further options being non-curative; or with metastatic tumor and patient declines standard of care therapies and alternatives offered, at the discretion of the investigator
4. At least 28 days or 5 half-lives, since the last dose of medication to treat their malignancy.
5. Measurable or evaluable disease by RECIST version 1.1
6. Capable of understanding and complying with protocol requirements
7. A life expectancy of greater than 12 weeks at Screening
8. ECOG Performance Status of 0 to 2
9. Written informed consent from the patient or the patient's legally acceptable representative prior to the initiation of any study procedures

10. Adequate bone marrow, liver, and renal function at screening as defined below:

    • hemoglobin ≥8.0 g/dL (transfusions allowed)
    • total lymphocyte count ≥500/µL
    • 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 subjects with known hepatic metastases
    • total serum bilirubin ≤1.5 x the ULN; ≤2.0 x the ULN if liver metastases are present; subjects 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 m2 (using Cockcroft Gault formula)

Exclusion Criteria:

Subjects who meet any of the following criteria will not be eligible for participation in the study:

1. Pregnant or breast feeding
2. 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
3. Active, symptomatic central nervous system (CNS) metastases. Subjects 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 and the Medical Monitor approves subject inclusion
4. 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
5. Severe uncontrolled cardiac disease within 3 months of study entry, including unstable or new onset angina, myocardial infarction or cerebrovascular accident
6. Women of child-bearing potential who are unable or unwilling to use an acceptable method of contraception
7. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C (in USA: Known infection with human immunodeficiency virus [HIV], hepatitis B or hepatitis C that is not controlled and has any related symptoms)
8. Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
9. Systemic lupus erythematous (SLE), inflammatory bowel disease, primary Sjogren's syndrome, rheumatoid arthritis, systemic sclerosis, and granulomatosis with polyangiitis; and any other autoimmune condition that, in the opinion of the investigator, may increase the risk of trial participation or trial drug administration, unless reviewed and approved by the medical monitor.
10. Any hematopoietic malignancy
11. Have more than one primary cancer diagnosis within the last 3 years
12. Organ transplant or requiring immune suppression
13. Bullous pemphigoid and other autoimmune diseases of the dermal-epidermal junction; these include bullous pemphigoid, bullous SLE, liner IgA disease, epidermolysis bullosa acquisita, and other pemphigoid variants.

Contacts and Locations

Contacts

Contact: Yosef Refaeli; +1-720-859-3547; refaeli@taigabiotech.com

Contact: Vivienne Margolis; +972-52-4639634; vmargolis@taigabiotech.com

Locations

United States, California

The Angeles Clinic and Research Institute; Recruiting

Los Angeles, California, United States, 90025

Principal Investigator: Inderjit Mehmi, MD

Israel

Rabin Medical Center; Recruiting

Petach Tikva, Israel

Principal Investigator: Salomon Stemmer, MD

Sponsors and Collaborators

Taiga Biotechnologies, Inc.

More Information

• Responsible Party: Taiga Biotechnologies, Inc.
• ClinicalTrials.gov Identifier: NCT04640246
• Other Study ID Numbers: TBX-3400-003
• First Posted: November 23, 2020
• Last Update Posted: February 2, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Taiga Biotechnologies, Inc.:

Cancer; Solid tumor; Malignant; Refractory; Resistant

Additional relevant MeSH terms:

Neoplasms