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

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.

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.

Inclusion Criteria:

• Subject should understand, sign, and date the written ICF prior to screening.
• Male or female aged 18 years or older.
• Subjects must have at least 1 measurable target lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy ≥ 3 months in the opinion of the investigator.
• Adequate organ function and bone marrow function as indicated by the following screening assessments performed within 14 days prior to the first dose of study treatment

Exclusion Criteria:

• Known allergy or hypersensitivity to any component of the study treatment.
• Has a known additional malignancy that is progressing or has required active treatment.
• Has abnormal or inadequately controlled endocrine function.
• Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption of oral medication.
• Previous anti-cancer therapy, including chemotherapy (chemotherapy with nitrosourea or mitomycin should be at least 6 weeks prior to initiation of study treatment), radiotherapy, molecular targeted therapy, or other investigational drugs received ≤ 4 weeks; endocrine therapy ≤ 2 weeks or ≤ 5-half-lives (whichever is shorter) prior to initiation of study treatment.