NCT05761223

A Phase I/II, Open-label Study to Investigate the Safety, Tolerability, PK, and Preliminary Efficacy of FB849

A Phase I/II, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of FB849 Administered in Subjects With Advanced Solid Tumors Alone and in Combination With Pembrolizumab

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 151 (estimated)
• Sponsor: 1ST Biotherapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is the first-in-human, multicenter, open-label Phase I/II study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of FB849 alone and in combination with pembrolizumab in subjects with advanced solid tumors for whom no standard therapy is available.

Detailed description

The study will be conducted in 3 parts: Phase I dose-escalation part with FB849 monotherapy and Phase II dose-escalation and dose-expansion parts of FB849 in combination with pembrolizumab. The Phase Ia dose-escalation part will use an adaptive study design termed Bayesian optimal interval (BOIN) design to investigate the safety and tolerability of FB849, and determine the maximum tolerated dose (MTD) and preliminary recommended Phase II dose (RP2D) of FB849. A BOIN design is a hybrid of rule-based and model-based design, which has the flexibility of dose escalation and de-escalation and allows more subjects to be enrolled into the doses closest to the target toxicity rate. Phase IIa enrollment will be initiated after Stage 1 of Phase Ib is completed. The selected RP2D from the prior Phase Ib part and a dose level ≥ 1 dose lower than the RP2D of FB849 will be selected by the SMC and will be evaluated in combination with a standard dose of pembrolizumab. Dose escalation will follow a BOIN design, but with at least 6 subjects at each FB849 dose level. In the Phase IIb part of the study, subjects with Type A cancer, Type B cancer, or Type C cancer will be enrolled in 3 cohorts to evaluate FB849 at the RP2D in combination with a standard dose of pembrolizumab to provide assessments of safety and anti-tumor activity of FB849. Both Phase II parts will also explore the impact of FB849 on pharmacodynamics and metabolites when in combination with pembrolizumab. Enrollment to Phase IIb will follow a Simon's two -stage design enrollment. Subjects will be monitored for safety, tolerability, and preliminary efficacy throughout the study. Tumor response will be assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 approximately every 6 weeks (± 3 days) in the first 18 weeks, then every 9 weeks (± 7 days) thereafter until disease progression, using computed tomography or magnetic resonance imaging of the chest, abdomen/pelvis, and if clinically indicated additional assessments eg, craniocerebral imaging, bone scan. Treatment with FB849 will continue until the start of a new anti-cancer treatment, disease progression, subject refusal, unacceptable toxicity, death, lost to follow-up, etc, whichever occurs first. Subjects who discontinue treatment due to other reasons than disease progression will continue with tumor assessments as per protocol until disease progression, death, or starting a new anti-cancer treatment.

Conditions

• Advanced Solid Tumor

Interventions

Type	Name	Description
DRUG	Phase Ia dose-escalation part of FB849 Monotherapy	At a given level dose once daily
DRUG	Phase Ib dose-expansion of FB849 monotherapy	At recommended dose for expansion cohort once daily
DRUG	Phase IIb dose-escalation part of FB849 in Combination with Pembrolizumab	At recommended dose for expansion cohort once daily in combination with pembrolizumab
DRUG	Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type A cancer)	At recommended dose for expansion cohort once daily in combination with pembrolizumab
DRUG	Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type B cancer)	At recommended dose for expansion cohort once daily in combination with pembrolizumab
DRUG	Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type C cancer)	At recommended dose for expansion cohort once daily in combination with pembrolizumab

Timeline

• Start date: 2023-12-13
• Primary completion: 2026-06-01
• Completion: 2026-10-01
• First posted: 2023-03-09
• Last updated: 2025-08-17

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study