A Phase 1 Study of TGI-5 as Monotherapy and in Combination With Nivolumab in Subjects With Locally Advanced/Metastatic Solid Tumors

NCT07376707 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TGI5-T1-01
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, multicenter, open-label, two-parts, FIH study to evaluate the tolerability, safety, PK/PD, and preliminary antitumor activity of TGI-5 as monotherapy and in combination with Nivolumab in subjects with unresectable locally advanced/metastatic solid tumors. The study consists of two parts: TGI-5 monotherapy (Phase 1a: including a dose escalation part and a dose expansion part), TGI-5 in combination with a fixed dose of Nivolumab (Phase 1b: including a dose escalation part and a dose expansion part).

Conditions

Melanoma (Skin Cancer); HCC - Hepatocellular Carcinoma; NSCLC (Non-small Cell Lung Cancer); CRC (Colorectal Cancer)

Keywords

TGI-5; Locally Advanced/Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicity (DLT)

  The incidence of DLTs during the DLT assessment period

  First 28 days of treatment.

• Frequency and Severity of Adverse Events (AE)

  The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.

  Screening to 30 days from last dose

Secondary Outcomes (2)

• Pharmacokinetics of TGI-5

  Day 1 of dosing through 30 days post last dose

• Objective Response Rate (ORR)

  Approximately 2 years.

Study Arms (1)

Dose escalation of TGI-5 as monotherapy，Dose Escalation of TGI-5 in Combination with Nivolumab

EXPERIMENTAL

At the Phase 1a of this study, 0.01 mg/kg is proposed as the starting dose of TGI-5 as monotherapy for the FIH study. An accelerate titration and then traditional "3+3" dose escalation design will be used to explore the maximum tolerated dose (MTD)/optimal biological dose (OBD). Subjects will receive TGI-5 at the assigned dose regimen in combination with a fixed dose of Nivolumab (240 mg, IV infusion) Q2W, and the DLT assessment will be conducted in the subjects during the DLT evaluation period (Cycle 1).

Drug: TGI-5

Interventions

TGI-5 DRUG

Subjects will receive TGI-5 as monotherapy in Phase 1a by Q2W for 28-day cycles. Subjects will receive TGI-5 in combination with Nivolumab in Phase 1b by Q2W for 28-day cycles.

Also known as: Nivolumab

Dose escalation of TGI-5 as monotherapy，Dose Escalation of TGI-5 in Combination with Nivolumab

Eligibility Criteria

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

You may qualify if:

• \. Male or female subject age ≥18 years at the time of informed consent. 2. Phase 1a and dose escalation part of Phase 1b: Subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors, mainly but not limited to CRC, HCC, melanoma, NSCLC.
• Dose expansion part of Phase 1b:
• Cohort 1: Subjects with histologically or cytologically diagnosed unresectable locally advanced and/or metastatic CRC.
• Cohort 2: Subjects with histologically or cytologically diagnosed unresectable locally advanced and/or metastatic melanoma.
• Cohort 3: Subjects with histologically or cytologically diagnosed unresectable locally advanced and/or metastatic NSCLC.
• Cohort 4: Subjects with other histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors.
• \. Subjects should have documented progression of disease despite all standard therapy or are intolerant of all standard therapy, or for whom no effective standard therapy exists. (Standard therapies are defined as treatments recommended by local guidelines, including but not limited to, chemotherapy, radiation, target therapies based on mutation status, immunotherapy, and surgery in general).
• Dose expansion part of Phase 1b:
• Cohort 1: Subjects with unresectable locally advanced and/or metastatic CRC o At least 2 prior standard chemotherapy/therapy regimens are required with documented progression or intolerability to the treatment.
• Standard chemotherapy regimens include all the following ones (if eligible and no contraindication): Fluoropyrimidine-containing regimen, and/or oxaliplatin-containing regimen, and/or irinotecan-containing regimen (treatment with a FOLFIRINOX regimen will count as 2 regimens).
• With or without an anti-VEGF therapy (e.g., bevacizumab).
• At least one of the anti-EGFR monoclonal antibodies (cetuximab or panitumumab) for KRAS wild-type subjects if clinically indicated.
• For subjects with a known microsatellite instability high (MSI-H):
• Prior treatment with an at least 2 doses of approved or investigational immune checkpoint inhibitor is required with documented progression or intolerability to the treatment.
• Demonstrated disease progression after immune checkpoint inhibitor treatment as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Appendix 5). The initial evidence of disease progression is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.

You may not qualify if:

• \. Subject with known active central nervous system (CNS) primary tumor or metastases.
• Note: Subject with previously treated CNS primary tumor/metastases can participate provided they are clinically stable for at least 2 weeks, have no evidence of new or enlarging brain metastases, and there has been no increase in steroid dose for 14 days prior to the first dose of TGI-5 to manage CNS symptoms. Subjects with carcinomatous meningitis or leptomeningeal spread, or spinal cord compression are excluded regardless of clinical stability.
• \. History of intercurrent severe chronic or active infections:
• Subjects with active hepatitis B, defined as: if hepatitis B virus surface antigen (HbsAg) positive, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) assay should be performed, and HBV DNA is above the limit quantification.
• Subjects with active hepatitis C, defined as: if hepatitis C virus (HCV) antibody positive, HCV ribonucleic acid (RNA) assay should be performed, and HCV RNA is positive.
• Known history of acquired immune deficient syndrome (AIDS) or human immunodeficiency virus (HIV) infection.
• Subjects with HIV infection may be eligible if CD4+ T cell counts ≥350 cells/µL and without a history of AIDS-defining opportunistic infections.
• Other severe chronic within 4 weeks prior to the first dose of TGI-5, including but not limited to hospitalization for complications of infection, bacteremia, severe pneumonia, or active tuberculosis. Or uncontrolled active infections or unexplained fever \>38°C within 7 days prior to first dose of TGI-5.
• \. Has a history of active autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study drug.
• With the following exceptions: clinically stable autoimmune thyroid disease; treatment with inhaled or topical corticosteroids such as ocular, intra-articular, and intranasal ≤10 mg daily of prednisone equivalent; short-term use of corticosteroids (no more than 7 days) for prophylaxis (e.g., to prevent contrast medium allergy or non-autoimmune allergic diseases); and replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes, physiologic corticosteroid replacement for adrenal or pituitary insufficiency).
• \. Has a history of symptomatic interstitial lung disease. 5. Toxicities of prior therapies have not been resolved to Grade ≤1 or baseline as per NCI-CTCAE v5.0, except for alopecia, skin hyperpigmentation, Grade 2 neuropathy and Grade 2 endocrinopathy that is well controlled by replacement therapy.
• \. Subjects with severe or uncontrolled cardiovascular disorder requiring treatment, including any of the following:
• New York Heart Association (NYHA) class III or IV congestive heart failure.
• Left ventricular ejection fraction (LVEF) \<50% assessed by multiple-gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Mean ECG QT interval corrected by Fridericia's formula (QTcF) \>480 milliseconds (ms) obtained from triplicate 12-lead ECGs, or congenital long QT syndrome.

Sponsors & Collaborators

• Hefei TG ImmunoPharma Co., Ltd.: lead
• Tigermed Consulting Co., Ltd: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Melanoma; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal 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; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hongxia Wang, Doctorate

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hang Zhou, Bachelor

CONTACT

+86-0551-62861151; hang.zhou@tgimmunopharma.com

Xiaohu Zheng, Doctorate

CONTACT

+86-0551-62861151; xiaohu.zheng@tgimmunopharma.com

Study Design

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

Model Details: In Phase 1a, subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors. After screening, qualified subjects will be assigned to each cohort on a chronological basis. Subjects will receive TGI-5 at the assigned dose regimen (intravenous \[IV\] infusion), and the dose limiting toxicity (DLT) assessment will be conducted in the subjects during the DLT evaluation period (28 days after the first dose \[i.e., Cycle 1, Day 1\~Day 28\]). In Phase 1b dose escalation part, subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors. After screening, qualified subjects will be assigned to each cohort on a chronological basis. Subjects will receive TGI-5 at the assigned dose regimen in combination with a fixed dose of Nivolumab (240 mg, IV infusion) Q2W, and the DLT assessment will be conducted in the subjects during the DLT evaluation period (Cycle 1).

Study Record Dates

• First Submitted: January 21, 2026
• First Posted: January 29, 2026
• Study Start: June 12, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)