Safety, Tolerability and Pharmacokinetics of a Monoclonal Antibody Specific to B-and T-Lymphocyte Attenuator (BTLA) as Monotherapy and in Combination With an Anti-PD1 Monoclonal Antibody for Injection in Subjects With Advanced Malignancies

NCT04137900 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TAB004-01
• Study Type: interventional
• Target: 499
• Locations: 1 country
• Sites: 24

Brief Summary

The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected advanced solid malignancies, including lymphoma, and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of TAB004 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB004, 2) evaluate antitumor activity of TAB004 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB004 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB004. The exploratory objectives are to: 1) evaluate pharmacodynamic effects of TAB004 on its target receptor BTLA, as well as effects on the immune system; 2) evaluate biomarkers that may correlate with activity of TAB004 as monotherapy and in combination with toripalimab; 3) evaluate the utility of BTLA ligand, herpesvirus-entry mediator (HVEM), and additional exploratory biomarkers that could aid in selection of appropriate subjects for TAB004 monotherapy and in combination with toripalimab.

Conditions

Advanced Unresectable Solid Tumor; Metastatic Solid Tumor

Keywords

immunotherapy; BTLA; HVEM; check point inhibitor; solid tumor; non-small cell lung cancer; NSCLC; melanoma; lymphoma; monoclonal antibody; phase 1 trial

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Treatment-related adverse events as assessed by CTCAE v4.0

  2 years

Secondary Outcomes (17)

• Objective Response Rate (ORR) by RECIST 1.1

  2 years

• Duration of Response (DOR) by RECIST 1.1

  2 years

• Disease Control Rate (DCR) by RECIST 1.1

  2 years

• Time to response (TTR) by RECIST 1.1

  2 years

• Progression-free survival (PFS) by RECIST 1.1

  2 years

Other Outcomes (4)

• Correlation analysis of HVEM expression of tumor and ORR

  3 years

• Correlation analysis of HVEM expression of tumor and DCR

  3 years

• Correlation analysis of HVEM expression of tumor and PFS

  3 years

Study Arms (9)

TAB004 0.3 mg/kg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004

TAB004 1 mg/kg repeat dose every 21days up to 2 years

EXPERIMENTAL

Drug: TAB004

TAB004 3 mg/kg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004

TAB004 10 mg/kg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004

TAB004 200mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004

TAB004 20mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004; Drug: Toripalimab

TAB004 70mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004; Drug: Toripalimab

TAB004 200mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004; Drug: Toripalimab

TAB004 500mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB004; Drug: Toripalimab

Interventions

TAB004 DRUG

Recombinant humanized IgG4κ monoclonal antibody specific to BTLA for injection

Also known as: JS004

TAB004 0.3 mg/kg repeat dose every 21 days up to 2 years; TAB004 1 mg/kg repeat dose every 21days up to 2 years; TAB004 10 mg/kg repeat dose every 21 days up to 2 years; TAB004 200mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB004 200mg repeat dose every 21 days up to 2 years; TAB004 20mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB004 3 mg/kg repeat dose every 21 days up to 2 years; TAB004 500mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB004 70mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

Toripalimab DRUG

a human IgG4k monoclonal antibody that specifically binds to the programmed death 1 (PD-1)

Also known as: TAB001, JS001

TAB004 200mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB004 20mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB004 500mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB004 70mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

Eligibility Criteria

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

You may qualify if:

• \. Able to understand and willing to sign the Informed Consent Form;
• \. Male or female ≥ 18 years;
• \. Subjects with histologically or cytologically confirmed advanced unresectable or metastatic solid tumor, including lymphoma that have progressed following prior treatment. In Part A, subjects must have received, or be ineligible for or intolerant of all available approved or standard therapies known to confer clinical benefit including immunotherapy, or for whom no standard therapy exists; in Part B, subjects with advanced or metastatic solid tumors, including but not limited to lymphoma, melanoma, NSCLC, or other tumors with agreement of the Sponsor, who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit; In Part C, subjects must have received at least one line of therapy for advanced or metastatic disease but are not required to have received all standard therapies known to confer clinical benefit; In Part D, subjects with advanced or metastatic solid tumors that may include but not limited to lymphoma, melanoma, NSCLC, RCC or UC who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit.
• \. Measurable disease per RECISTv1.1 and iRECIST, or RECIL 2017 for lymphoma
• \. ECOG performance status of 0 or 1 with life expectancy of 3 months in the opinion of the investigator.
• \. Adequate organ and marrow function, as defined below:
• Hemoglobin 8.0 g/dL within first 2 weeks prior to first dose of TAB004 (are not requiring a transfusion within 14 days prior to dosing)
• Absolute neutrophil count (ANC) 1.0 x 109 /L (1,000 /mm3)
• Absolute lymphocyte count ≥ 0.6 x 109/L (600/mm3)
• Platelet count 75 x 109 /L (75,000 /mm3), and not requiring platelet transfusions within the 5 days prior to dosing
• Total bilirubin ≤ 1.5 x ULN except subjects with documented Gilbert's syndrome who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) or 24 hour urine CrCl ≥ 40 mL/minute Cockcroft-Gault formula will be used to calculate CrCl. 24-hour urine CrCl will be derived using the measured creatinine clearance formula
• International normalized ratio (INR) ≤ 2.0 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN; applies only to subjects who do not receive therapeutic anticoagulation; subjects receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose
• \. Willingness to provide consent for biopsy samples (In Part A, fresh pre-treatment biopsies will be requested from subjects with safely accessible lesions. For subjects who cannot provide a fresh pre-treatment biopsy, request for the most recent accessible archival specimen will be required. In Part B, C and D, fresh pre-treatment biopsies will be required from subjects with safely accessible lesions. The most recent archival specimens will also be requested).

You may not qualify if:

• \. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
• \. Any concurrent anti-cancer therapy, such as but not limited to chemotherapy, targeted therapy, radiotherapy, immunotherapy, or biologic therapy. Radiation treatment for palliative intent is allowed provided that lesions other than those receiving radiation are available to measure response. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for type 2 diabetes and hormone replacement therapy) is acceptable.
• Note: Local treatment of isolated lesions for palliative intent is acceptable (e.g., by local surgery or radiotherapy).
• \. Current or prior use of immunosuppressive medication within 2 weeks prior to the first dose of TAB004, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10 mg/day of prednisone or equivalent.
• \. Prior exposure to anti-BTLA, or anti-HVEM antibodies for subjects enrolled into Part A and B only; prior treatment with anti-PD-1 or anti-PDL-1is allowed,including toripalimab for all subjects.
• \. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• \. Subjects with another malignancy, or history or other malignancy within 3 years that is not expected to relapse. Subjects with non-melanomatous skin cancer or cervical cancer that has been curatively surgically resected are eligible.
• \. Major surgery (as defined by the investigator) within 28 days prior to first dose of TAB004 or has not recovered to at least Grade 1 from adverse effects from such procedure, or anticipation of the need for major surgery during study treatment.
• \. Active or prior documented autoimmune disease, such as but not limited to systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis, autoimmune vasculitis, autoimmune neuropathies or type 1 insulin-dependent diabetes mellitus.
• Note: Subjects with the following are not excluded: vitiligo; alopecia; Grave's disease not requiring systemic treatment other than thyroid hormone replacement (within the past 2 years) psoriasis not requiring systemic treatment; controlled celiac disease; subjects with a history of autoimmune hypothyroidism requiring only thyroid hormone replacement therapy; And type 2 diabetes, provided that it is adequately controlled.
• \. Clinically significant (intracranial, gastrointestinal) bleeding within 2 weeks prior to screening.
• \. Known history of tuberculosis.
• \. Subjects with history of or current drug-induced interstitial lung disease or pneumonitis ≥ Grade 2.
• \. Subjects who have discontinued prior immune therapy due to immune mediated adverse reaction(s).
• \. Subjects who are known to be human immunodeficiency virus positive.

Sponsors & Collaborators

• TopAlliance Biosciences: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (24)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of Arizona College of Medicine-Tucson

Tucson, Arizona, 85721, United States

RECRUITING

UCLA Health Westwood Cancer Care

Los Angeles, California, 90095, United States

RECRUITING

University of California Irvine (UCI) Medical Center

Orange, California, 92868, United States

RECRUITING

University of California San Francisco (UCSF) Medical Center-Mission Bay

San Francisco, California, 22902, United States

RECRUITING

University of California at San Francisio

San Francisco, California, 94158, United States

RECRUITING

Boca Raton Clinical Research (BRCR)

Boca Raton, Florida, 33432, United States

WITHDRAWN

Winship Cancer Institute at Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Iowa Hospitals

Iowa City, Iowa, 52242, United States

RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

SUSPENDED

Northwell Health

New Hyde Park, New York, 11042, United States

NOT YET RECRUITING

New York Presbyterian / Weill Cornell Medical Center

New York, New York, 10021, United States

ACTIVE NOT RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

ACTIVE NOT RECRUITING

UC Health - University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

SUSPENDED

The Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

ACTIVE NOT RECRUITING

University of Texas Southwestern Medical Center Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, 75390-8565, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Melanoma; Lymphoma

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sheng Yao, PhD

  TopAlliance Biosciences, Inc.

  STUDY DIRECTOR

Central Study Contacts

Richard Curry, MD

CONTACT

800-753-2389; rcurry@ctifacts.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

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 24, 2019
• Study Start: October 30, 2019
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 5, 2024

Record last verified: 2024-02

Locations

US (24)