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

Recruiting now · Phase 1

Conditions studied: CRC (Colorectal Cancer), Melanoma (Skin Cancer), HCC - Hepatocellular Carcinoma, NSCLC (Non-small Cell Lung Cancer)

In brief

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).

Key facts

Study ID

NCT07376707

Run by

Hefei TG ImmunoPharma Co., Ltd.

People needed

194

Starts

2025-06-12

Expected to finish

2027-12-31

Last updated by the study team

2026-01-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 1. 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.
• Progressive disease that has been documented within 12 weeks from the last dose of immune checkpoint inhibitor.
• Note: a line of therapy is generally considered >2 cycles of exposure to the same regimen followed by radiographically documented progression. Agents that are mechanistically similar (e.g., 5-fluorouracil and capecitabine) and are used interchangeably due to tolerability but not progression may be considered as components of the same regimen upon discussion with the medical monitor.
• Subjects must have progressed while receiving or after of the last administration of their last line of standard therapy or be unable to tolerate any of these standard treatments.
• Subjects who progressed on/within 3 months of adjuvant therapy with anti-PD-1 antibody will be allowed; subjects who received adjuvant chemotherapy and had recurrence/progression with development of unresectable or metastatic disease during or within 6 months of completion of the adjuvant chemotherapy can count this as a line of therapy.
• Cohort 2: Subjects with anti-PD-(L)1 antibody PD-1 relapsed/refractory melanoma
• PD-1 refractory disease as defined as progression on treatment with anti-PD-1 antibody administered either as monotherapy or in combination with other checkpoint inhibitors (anti-CTLA4 antibody or anti-LAG-3 antibody) or other therapies. Anti-PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved or investigational anti-PD-1 antibody with documented progression or intolerability to the treatment.
• Demonstrated disease progression after anti-PD-1 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.
• Progressive disease that has been documented within 12 weeks from the last dose of anti-PD-1 antibody.
• Subjects who progressed on/within 3 months of adjuvant therapy with anti-PD-1 antibody will be allowed; an adjuvant therapy will count as 1 prior line of therapy if received within the prior 6 months.

You may not qualify if…

• 1. 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.
• Any of the following within 6 months prior to screening: Grade >2 ventricular arrhythmia, myocardial infarction, severe/unstable angina (even if controlled with medication), coronary artery bypass graft, congestive heart failure, cerebrovascular accident, or transient ischemic attack.
• Presence of uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg). Subjects with a history of hypertension are allowed if blood pressure is controlled to within these limits by anti-hypertensive treatment.
• Symptomatic pulmonary embolism within 6 months prior to initiation of study treatment.
• Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years (Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and localized prostate cancer who have undergone potentially curative therapy. These subjects are not excluded).
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as severe combined immunodeficiency disease (SCID).
• Concurrent opportunistic infection. 10. Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (monthly or more frequently).
• Previously treated with the following antitumor therapy (prior to the first dose of TGI-5):
• Previous treated with TIGIT-targeting therapy. 2) Chemotherapy, target therapy, immunotherapy, or other anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment, except:

Where it is running

• Fudan University Shanghai Cancer Center — Shanghai, China (enrolling)

Full record on ClinicalTrials.gov

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