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

Advanced Solid Tumor Clinical Trial

Official title: An Open-label, Dose Escalation and Dose Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of STI-7349 in Subjects With Advanced Solid Tumors

Status Recruiting

Clinical Trial Summary

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) and dose expansion for STI-7349 in combination with Pembrolizumab (2B). In Part 2A, a dose escalation study of STI-7349 in combination with Pembrolizumab 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, and to determine the RP2D of STI-7349 in combination with Pembrolizumab; in Part 2B, an expansion study of STI-7349 in combination with Pembrolizumab or add standard treatment on the basis of STI-7349 combined with pembrolizumab will be conducted in target tumor types that may potentially benefit to assess the safety and preliminary efficacy of the combination.

Clinical Trial Description

Period I: Dose escalation of STI-7349 alone (1A) 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 1A of this trial will use rapid titration and a traditional 3 + 3 trial 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) 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. Period II: Dose expansion for STI-7349 in combination with Pembrolizumab (2B) According to the data from the 2A 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 2A 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. ;

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

• NCT number: NCT05978102
• Study type: Interventional
• Source: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
• Contact: Wang
• Phone: 13957158572
• Email: Doctorhuxi@163.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 23, 2023
• Completion date: December 2025