NCT07376707

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

A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of TGI-5 as Monotherapy and in Combination With Nivolumab in Subjects With Locally Advanced/Metastatic Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 194 (estimated)
• Sponsor: Hefei TG ImmunoPharma Co., Ltd. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

In Phase 1a, subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors, mainly but not limited to CRC, hepatocellular carcinoma (HCC), melanoma, and NSCLC who have progressed despite all standard therapy or are intolerant of all standard therapy, or for whom no effective standard therapy exists will be enrolled. 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 \[i.e., Cycle 1, Day 1\~Day 28\]). Subjects who experience a DLT will permanently discontinue the study treatment and be closely monitored until the toxicity has resolved to Grade 1 or baseline or as long as the investigator considers it stable and unsolvable. After 28-day of DLT evaluation period, subjects who did not experience a DLT will continue to receive TGI-5 as monotherapy at the same dose level once every 2 weeks (Q2W) until discontinuation of treatment for any reason, such as confirmed progressive disease, unacceptable toxicity, initiation of a new anticancer therapy, death, lost follow-up, withdrawal of informed consent, or at the discretion of the investigator due to safety or compliance, whichever occurs first. 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). After the OBD is determined by the safety monitoring committee (SMC), the corresponding cohort will be expanded at the OBD dose level for further assessment of safety, PK/PD, and antitumor activity. About 10\~20 subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors, mainly but not limited to CRC, HCC, melanoma, and NSCLC who have progressed despite all standard therapy or are intolerant of all standard therapy, or for whom no effective standard therapy exists will be enrolled. After the primary analysis of Phase 1a, the SMC will discuss and decide whether the study can proceed to Phase 1b based on data available from Phase 1a. The proposed starting dose of TGI-5 in combination with Nivolumab will be at least 2 dose levels below the MTD/OBD identified for TGI-5 as a single agent in Phase 1a. The starting dose of TGI-5 in combination with Nivolumab will be selected by the SMC based on the available safety, tolerability, PK/PD, and antitumor activity data from the previous monotherapy phase (Phase 1a), non-clinical studies of combined administration will also be considered comprehensively. The dose of Nivolumab is selected as fixed dose (240 mg) Q2W, which is consistent with the dosing interval of TGI-5. The "3+3" design and definition of MTD are the same as that in Phase 1a. Definition of recommended phase 2 dose (RP2D) is the same as OBD in Phase 1a. In Phase 1b dose escalation part, subjects with histologically or cytologically diagnosed unresectable locally advanced/metastatic solid tumors, mainly but not limited to CRC, HCC, melanoma, and NSCLC who have progressed despite all standard therapy or are intolerant of all standard therapy, or for whom no effective standard therapy exists will be enrolled. 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). When TGI-5 and Nivolumab are administered on the same day, it is recommended that TGI-5 be administered first. After 28-day of DLT evaluation period, subjects who did not experience a DLT will continue to receive the combination regimen until discontinuation of treatment for any reason, such as confirmed progressive disease, unacceptable toxicity, initiation of a new anticancer therapy, death, lost follow-up, withdrawal of informed consent, or at the discretion of the investigator due to safety or compliance, whichever occurs first. Treatment cycles will occur consecutively without interruption unless an AE leading to treatment interruption occurs. Subjects who experience a DLT will permanently discontinue study treatment (both TGI-5 and Nivolumab) and be closely monitored until the toxicity has resolved to Grade 1 or baseline or if the investigator considers it stable and unsolvable. Once the MTD and/or RP2D of TGI-5 in combination regimen is identified and the safety profile has been reviewed by the SMC and is considered safe and tolerable for subjects based on the available data, the dose expansion part of Phase 1b in the study will start. Subjects who meet eligibility criteria are planned to be enrolled into 4 cohorts based on their tumor types to evaluate the efficacy and safety of TGI-5 in combination with Nivolumab. At least 2 dosages will be evaluated and compared in each cohort of dose expansion part to identify an optimal dosage as the RP2D. The dose expansion phase will consist of 4 cohorts tentatively designated as: * Cohort 1: Unresectable locally advanced/metastatic CRC * Cohort 2: Unresectable locally advanced/metastatic melanoma * Cohort 3: Unresectable locally advanced/metastatic NSCLC * Cohort 4: Other Unresectable locally advanced/metastatic solid tumors

Conditions

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

Interventions

Type	Name	Description
DRUG	TGI-5	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.

Timeline

• Start date: 2025-06-12
• Primary completion: 2027-10-31
• Completion: 2027-12-31
• First posted: 2026-01-29
• Last updated: 2026-01-29

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study