A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics/ Pharmacodynamics, and Antitumor Activity of TGI-6 as Monotherapy in Subjects With Locally Advanced/Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- TGI-6 Injection
- Conditions
- Advanced or Metastatic Solid Tumors
- Sponsor
- Hefei TG ImmunoPharma Co., Ltd.
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- Dose-Finding
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
A Phase 1 Study to Evaluate TGI-6 in Subjects with Locally Advanced/Metastatic Solid Tumors
Detailed Description
This is a Phase 1, multicenter, open-label, two-parts, FIH study to evaluate the tolerability, safety, PK/PD, and preliminary anti-tumor activity of TGI-6 as monotherapy in subjects with unresectable locally advanced/metastatic CRC, or subjects with confirmed B7-H6-positive locally advanced/metastatic solid tumors. The study consists of two parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b). For each subject in the two parts, the study will include a screening period (up to 28 days), a treatment period (until treatment discontinuation), and a follow-up period including safety and survival follow-up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects age ≥18 years at the time of informed consent.
- •Phase 1a: Subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic CRC. Or subjects with confirmed B7-H6-positive unresectable locally advanced/metastatic solid tumors, mainly but not limited to TNBC, HCC, HNSCC, SCLC, OC, GC, pancreatic cancer, and melanoma.
- •Phase 1b Cohort 1: Subjects must have pathologically documented, definitively diagnosed unresectable locally advanced and/or metastatic CRC.
- •Phase 1b Cohort 2: Subjects must have pathologically documented, definitively diagnosed unresectable locally advanced and/or metastatic solid tumors with B7-H6-positive, mainly but not limited to TNBC, HCC, HNSCC, SCLC, OC, GC, pancreatic cancer, and melanoma.
- •Phase 1a or Phase1b Cohort 2: Subjects should have progressed despite all standard therapy or be intolerant of all standard therapy, or for whom no 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).
- •All subjects except subjects with CRC must agree to the collection of tumor samples for confirmation of B7-H6 expression status in a central lab.
- •Subjects in Phase 1a must have at least one evaluable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Subjects in Phase 1b must have least one measurable lesion as defined per RECIST v1.1 which has not received radiotherapy (or progressive disease after radiotherapy).
- •ECOG PS (Appendix 5) of 0\~
- •Life expectancy ≥3 months.
Exclusion Criteria
- •Subject with known active central nervous system (CNS) primary tumor or metastases.
- •History of intercurrent severe chronic or active infections.
- •Has a history of active autoimmune diseases .
- •Has a history of symptomatic interstitial lung disease.
- •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.
- •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 .
- •Evidence of clinically significant immunosuppression .
- •Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures .
Arms & Interventions
TGI-6 Injection
TGI-6 monotherapy dose escalation(Phase 1a) . TGI-6 monotherapy dose expansion(Phase 1b) .
Intervention: TGI-6 Injection
Outcomes
Primary Outcomes
Dose-Finding
Time Frame: Approximately 3 years.
Determination of the MTD or maximum tested dose, and the RP2D.
Dose-limiting Toxicity (DLT)
Time Frame: First 21 days of treatment.
The incidence of DLTs during the DLT assessment period.
Frequency and Severity of Adverse Events (AE)
Time Frame: Screening to 30 days from last dose
The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.
Secondary Outcomes
- Number of subjects with Anti-TGI-6 antibody positive(Day 1 of dosing through 7 days post last dose)
- Objective Response Rate (ORR)(Approximately 3 years.)
- Overall Survival (OS)(Approximately 3 years.)
- Pharmacokinetics of TGI-6(Day 1 of dosing through 7 days post last dose)
- Duration of Response (DoR)(Approximately 3 years)
- Disease Control Rate (DCR)(Approximately 3 years.)
- Progression Free Survival (PFS)(Approximately 3 years.)