A Dose Escalation and Dose Expansion Clinical Study of STI-7349 in Subjects With Advanced Solid Tumors

Advanced Solid Tumor

This is a first-in-human, Phase Ⅰ, open-label, 2-period dose escalation and expansion study of STI-7349 administered intravenously to subjects with advanced solid tumors: * Period I is divided into two parts: Dose escalation for STI-7349 alone (1A) and dose expansion for STI-7349 alone (1B). In Part 1A, a rapid titration approach and traditional 3 + 3 trial design will be used to assess the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), PK/biomarker profile, and to determine the recommended Phase 2 dose (RP2D) of STI-7349 alone; in Part 1B, an expansion study of STI-7349 alone will be conducted in target tumor types that may potentially benefit to assess the safety and preliminary efficacy of STI-7349 alone. * Period Ⅱ is divided into two parts: Dose escalation for STI-7349 in combination with Pembrolizumab (2A) or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) and dose expansion for STI-7349 in combination with Pembrolizumab (2B) or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.). In Part 2A, a dose escalation study of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) is planned to be conducted using ½ RP2D of STI-7349 alone as the starting dose, which will use a traditional 3 + 3 trial design to assess the safety, DLTs, MTD, PK/biomarker profile of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) , and to determine the RP2D of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) ; in Part 2B, an expansion study of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) or add standard treatment on the basis of STI-7349 combined with pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) will be conducted in target tumor types that may potentially benefit to assess the safety and preliminary efficacy of the combination.

Period I: Dose escalation of STI-7349 alone (1A) Periond 1A1 part: According to the preclinical trial data, 1mg was used as the initial dose and the accelerated titration test design was adopted. If no adverse events have occurred as specified in the following acceleration titers, the dose increment ratio of 60%, 50%, 50%, 33.3%, 25% is recommended by the modified Fibonacci method. The six initial dose groups of STI-7349 were 1mg, 1.6mg, 2.4mg, 3.6mg, 4.8mg and 6.0 mg.respectively. Eligible subjects will be placed into 6 dose groups in sequence from low to high dose. Subjects in all dose groups will receive 21 days per dosing cycle and Day 1 of each cycle will be the dosing day. Part 1A1 of this trial will use rapid titration and a traditional 3 + 3 trial design. Periond 1A2 part: According to the preliminary clinical trial data available , the terminal elimination half-life of HSA-IL2v in humans is approximately 23 hours. With reference to the modified Fibonacci method, the dose escalation ratio is set at 60%. Therefore, two preliminary dose levels for STI-7349 escalation have been established: 1 mg and 1.6 mg. Eligible subjects will be sequentially enrolled into the two dose groups in ascending order. For all dose groups, each treatment cycle will last 28 days, with dosing administered on Day 1 and Day 15 of each cycle. The Part 1A2 of this trial will adopt the conventional 3+3 study design. Period I: Dose expansion of STI-7349 alone (1B) Based on data from the 1A escalation period, target tumor types with potential benefit are selected, and subjects are expanded to 20 to 30 at the RP2D of STI-7349 alone to conduct an expansion study of STI-7349 alone to further assess the safety and preliminary efficacy of the RP2D of STI-7349 alone. STI-7349 will be administered at the same frequency as that in Part 1A and continued until the maximum 2-year dosing period, disease progression/relapse, death, intolerable toxicity, inability of the subject to benefit from study treatment as judged by the investigator, withdrawal from clinical study treatment by the subject or his/her legal representative, loss to follow-up, or completion of the entire study, whichever comes first. Period II: Dose escalation for STI-7349 in combination with Pembrolizumab (2A) Periond 2A1 part: According to the single-agent RP2D of STI-7349 determined in phase I, the dose of STI-7349 combined with palibrizumab was increased in subjects with advanced solid tumors. ≤ ½RP2D of STI-7349 single agent was used as the starting dose of the combined dose increase, and the expected RP2D dose was 4.8mg. The initial dose of combined administration was ≤2.4mg. The approved standard therapeutic dose of pabolizumab is 200mg IV. According to the results of the Phase I study, the three dose groups of STI-7349 combined with pabolizumab were initially set as 1mg, 1.6mg and 2.4mg, respectively. Qualified subjects will be selected into 3 dose groups in sequence from low to high dose. Periond 2A2 part: According to the single-agent RP2D of STI-7349 determined in phase I, the dose of STI-7349 combined with other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) was increased in subjects with advanced solid tumors. 1mg (≤ ½RP2D of STI-7349 single agent) was used as the starting dose of the combined dose increase. The investigator will refer to the CSCO or other current guidelines or appropriate drug inserts to determine the dose and dosing schedule of other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.). According to the results of the Phase I study, the two dose groups of STI-7349 combined with other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) were initially set as 1mg, 1.6mg, respectively. Qualified subjects will be selected into 2 dose groups in sequence from low to high dose. Period II: Dose expansion for STI-7349 in combination with Pembrolizumab (2B) Periond 2B1 part: According to the data from the 2A1 escalation period, target tumor types with potential benefit are selected, and subjects are expanded to 20 to 30 at the RP2D of the combination to conduct a dose expansion study of STI-7349 in combination with Pembrolizumab or add standard treatment on the basis of STI-7349 combined with pembrolizumab to further assess the safety and preliminary efficacy of the RP2D of the combination. STI-7349 will be administered at the same frequency as that in Part 2A1 and continued until the maximum 2-year dosing period, disease progression/relapse, death, intolerable toxicity, inability of the subject to benefit from study treatment as judged by the investigator, withdrawal from clinical study treatment by the subject or his/her legal representative, loss to follow-up, or completion of the entire study, whichever comes first. Periond 2B2 part：According to the data from the 2A2 escalation period, target tumor types with potential benefit are selected, and subjects are expanded to 20 to 30 at the RP2D of the combination to conduct a dose expansion study of STI-7349 in combination with with other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) or add standard treatment on the basis of STI-7349 combined with with other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) to further assess the safety and preliminary efficacy of the RP2D of the combination. STI-7349 will be administered at the same frequency as that in Part 2A2 and continued until the maximum 2-year dosing period, disease progression/relapse, death, intolerable toxicity, inability of the subject to benefit from study treatment as judged by the investigator, withdrawal from clinical study treatment by the subject or his/her legal representative, loss to follow-up, or completion of the entire study, whichever comes first.

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