A Clinical Study of TAB006 in Patients With Previously Treated, Advanced Malignancies

NCT05253105 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: TAB006-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective is to assess the safety and tolerability of TAB006 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 TAB006 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB006, 2) evaluate antitumor activity of TAB006 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB006 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB006.

Conditions

Previously Treated, Advanced; Malignancies

Keywords

immunotherapy; advance malignancies; monoclonal antibody; phase 1 trial

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of multiple doses of TAB006 in combination with toripalimab.

  The endpoints for characterization of safety and tolerability will be characterized by all of the following: the incidence and severity of dose limiting toxicity (DLT); immune-related and other adverse events (AEs) and serious adverse events (SAEs) graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0; incidence and severity of laboratory abnormalities, to include electrocardiogram (ECG) results, and abnormal findings on physical examination.

  from first treatment visit thru 90 days post last treatment

• To establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of TAB006 when administered in combination toripalimab 240 mg Q3W.

  from first treatment visit thru 90 days post last treatment

Secondary Outcomes (13)

• Maximum Observed Concentration (Cmax)

  from first treatment visit thru 90 days post last treatment

• Minimum Observed Concentration (Cmin)

  from first treatment visit thru 90 days post last treatment

• Time to Reach Maximum Concentration (Tmax)

  from first treatment visit thru 90 days post last treatment

• Area Under the Concentration-time Curve (AUC)

  from first treatment visit thru 90 days post last treatment

• Volume of Distribution (Vss)

  from first treatment visit thru 90 days post last treatment

Other Outcomes (2)

• TIGIT receptor occupancy (RO) in peripheral blood mononuclear cells (PBMC) and tumor

  from first treatment visit thru 90 days post last treatment

• To evaluate biomarkers that may correlate with anti-tumor activity of TAB006 when administered with toripalimab.

  from first treatment visit thru 90 days post last treatment

Study Arms (6)

TAB006 60mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB006; Drug: Toripalimab

TAB006 240mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB006; Drug: Toripalimab

TAB006 600mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB006; Drug: Toripalimab

TAB006 1800mg and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB006; Drug: Toripalimab

Dose Expansion / TAB006 RP2D and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB006; Drug: Toripalimab

Indication Specific / TAB006 RP2D and Torpalimab 240mg repeat dose every 21 days up to 2 years

EXPERIMENTAL

Drug: TAB006; Drug: Toripalimab

Interventions

TAB006 DRUG

Recombinant humanized, IgG4κ (immunoglobulin gamma 4, kappa) monoclonal antibody (mAb) that specifically binds to the T cell immunoreceptor with Ig and ITIM domains (TIGIT))

Also known as: JS006

Dose Expansion / TAB006 RP2D and Torpalimab 240mg repeat dose every 21 days up to 2 years; Indication Specific / TAB006 RP2D and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 1800mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 240mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 600mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 60mg 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: JS001, TAB001

Dose Expansion / TAB006 RP2D and Torpalimab 240mg repeat dose every 21 days up to 2 years; Indication Specific / TAB006 RP2D and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 1800mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 240mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 600mg and Torpalimab 240mg repeat dose every 21 days up to 2 years; TAB006 60mg 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;
• \. Histopathologically or cytologically confirmed advanced solid tumors and advanced lymphoma. In the Dose Escalation and Dose Expansion Phases, both Parts A and B, patients must have disease progression on standard therapy, or be ineligible for or intolerant of available approved standard therapies known to confer clinical benefit (including immunotherapy) or for whom no effective standard therapy exists. In the Indication-specific Expansion Phase, patients must have disease progressed after at least one prior line of standard therapy;
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1and expected survival ≥12 weeks;
• \. At least one measurable lesion per RECISTv1.1 or 2014 Lugano Classification;
• \. Ability to provide an archived tumor sample obtained within the past 2 years or agreement to undergo a pre-treatment biopsy from safely accessible lesions to provide a tumor sample if such an archived specimens cannot be provided. For patients who cannot provide a fresh pre-treatment biopsy, and a recent sample from the past 2 years is not available, the most recent accessible archival specimen will be required;
• \. Adequate organ and marrow function, as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5×109/L (1,500/mm3) with no administration of hematopoietic growth factors for at least 14 days prior to the planned first dose of TAB006;
• Lymphocyte count ≥ 600/mm3;
• Platelet (PLT) ≥ 100×109/L (100,000/mm3) with no administration of hematopoietic growth factors or platelet transfusions at least 14 days prior to the planned first dose of TAB006;
• Hemoglobin (Hb) ≥9 g/dL with no administration of hematopoietic growth factors or red blood cell transfusions for at least 14 days prior to the planned first dose of TAB006;
• Total bilirubin (TBIL) ≤ 1.5 times (x) the ULN; for patients with liver metastasis or Gilbert syndrome, TBIL ≤ 3 x ULN;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN in patients without liver metastases and ALT and AST ≤ 5 × ULN for patients with liver metastases at baseline;
• Blood creatinine (Cr) ≤ 1.5 x ULN, calculated creatinine clearance (Cockcroft-Gault formula) ≥ 40 mL/min, or 24-h urine creatinine clearance ≥ 40 mL/min;
• Left ventricular ejection fraction ≥ 50%;

You may not qualify if:

• \. Concurrent enrollment in another clinical study or participation in another clinical study within 28 days prior to the first dose of TAB006 except for observational (non- interventional) studies or the follow-up period of an interventional study;
• \. Current or prior use of systemic anticancer therapy, including but not limited to chemotherapy, immunotherapy, biologic therapy, hormone therapy, and targeted therapy within 28 days prior to the first dose of TAB006; except for nitrosoureas and mitomycin which may not have been administered within 6 weeks prior to the first dose of TAB006) unless toxicities from prior anticancer therapy (other than alopecia or autoimmune endocrinopathy that is clinically stable on hormone replacement therapy) have not improved to baseline or Grade 0 or 1 toxicity. Consult the Medical Monitor regarding enrollment of patients with toxicity that is irreversible (e.g., ototoxicity, visual loss) and unlikely to be exacerbated by TAB006 or toripalimab);
• \. Concurrent or prior radiotherapy within 28 days prior to the first dose of TAB006 or unresolved treatment-related radiation toxicity. Limited local radiotherapy for palliative intent (e.g., to a single site of metastatic disease) is permitted within 28 days prior to the first dose of TAB006 provided that the patient has no evidence of or had recovered from any treatment-related radiation toxicity;
• \. Prior exposure to monoclonal antibodies targeting TIGIT or any of its ligands, including CD155, CD112, or CD113;
• \. History of immune-related AE resulting in discontinuation of prior immunotherapy.
• \. Major surgery within 28 days prior to the first dose of TAB006 or still recovering from prior surgery;
• \. Symptomatic or untreated central nervous system metastases, including leptomeningeal metastases, requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids. Patients with previously treated brain metastases may be eligible provided that they have been clinically stable for at least 28 days prior to the first dose of TAB006, without evidence of new or enlarging CNS metastases, and on less than 10 mg prednisone daily (or prednisone equivalent);
• \. Use of therapeutic immunosuppressive medication (e.g., prednisone dose of ≥10 mg/day or equivalent, TNF inhibitors) within 28 days prior to the first planned dose of TAB006. This does not include intranasal and inhaled corticosteroids or physiologic replacement doses of systemic corticosteroids;
• \. Moderate to severe hypersensitivity reaction to toripalimab or other PD-1 blocking antibodies;
• \. Prior allogeneic bone marrow transplantation or prior solid organ transplantation;
• \. Receipt of live attenuated vaccination within 30 days prior to the first dose of TAB006. For non-live vaccines, it is recommended that the vaccine not be administered within 48 hours prior to through 21 days after the first dose in Cycle 1;
• \. Patients with another malignancy that has not been curatively treated are not eligible. Patients with curatively treated malignancy within the past 3 years prior to the first dose of TAB006, with an expected three-year recurrence rate of ≥ 30% are not eligible;
• \. History of active autoimmune disease within the past 2 years, with the following exceptions: vitiligo, alopecia, endocrinopathies controlled by hormone replacement therapy, rheumatoid arthritis and other arthropathies that have not required immunosuppression other than non- steroidal anti-inflammatory agents, celiac disease controlled by diet, or psoriasis controlled with topical medication;
• \. History of primary immunodeficiency, other than selective IgA deficiency;
• \. Uncontrolled intercurrent diseases or conditions including, but not limited to:

Sponsors & Collaborators

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

MeSH Terms

Conditions

Neoplasms

Interventions

toripalimab

Study Officials

• Sheng Yao, PhD

  TopAlliance Biosciences, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 23, 2022
• Study Start: March 15, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 31, 2022

Record last verified: 2022-02