Trial Title:
A Phase I/II, Open-label Study to Investigate the Safety, Tolerability, PK, and Preliminary Efficacy of FB849
NCT ID:
NCT05761223
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
The study will be conducted in 4 parts: Phase I dose-escalation and dose-expansion parts
with FB849 monotherapy and Phase II dose-escalation and dose-expansion parts of FB849 in
combination with pembrolizumab.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Phase Ia dose-escalation part of FB849 Monotherapy
Description:
At a given level dose once daily
Arm group label:
Phase Ia dose-escalation part of FB849 Monotherapy
Other name:
FB849
Intervention type:
Drug
Intervention name:
Phase Ib dose-expansion of FB849 monotherapy
Description:
At recommended dose for expansion cohort once daily
Arm group label:
Phase Ib dose-expansion of FB849 monotherapy
Other name:
FB849
Intervention type:
Drug
Intervention name:
Phase IIb dose-escalation part of FB849 in Combination with Pembrolizumab
Description:
At recommended dose for expansion cohort once daily in combination with pembrolizumab
Arm group label:
Phase IIa dose-escalation part of FB849 in Combination with Pembrolizumab
Other name:
FB849
Other name:
KEYTRUDA®
Intervention type:
Drug
Intervention name:
Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type A cancer)
Description:
At recommended dose for expansion cohort once daily in combination with pembrolizumab
Arm group label:
Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type A cancer)
Other name:
FB849
Other name:
KEYTRUDA®
Intervention type:
Drug
Intervention name:
Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type B cancer)
Description:
At recommended dose for expansion cohort once daily in combination with pembrolizumab
Arm group label:
Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type B cancer)
Other name:
FB849
Other name:
KEYTRUDA®
Intervention type:
Drug
Intervention name:
Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type C cancer)
Description:
At recommended dose for expansion cohort once daily in combination with pembrolizumab
Arm group label:
Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type C cancer)
Other name:
FB849
Other name:
KEYTRUDA®
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 4 parts: Phase I dose-escalation and dose-expansion parts
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.
The Phase Ib dose expansion of FB849 monotherapy part will be initiated once the
preliminary RP2D has been determined in the Phase Ia part to provide assessment of safety
and anti-tumor activity of FB849 in subjects with advanced solid tumors. It will evaluate
FB849 at the preliminary RP2D. Based on data from the Phase Ia part, an additional dose ≥
1 dose lower than the preliminary RP2D may be evaluated if needed, as determined by the
safety monitoring committee (SMC). Subjects will be enrolled using a Simon's two-stage
enrollment. If more than 1 dose level cohort is evaluated, subjects will be randomized to
a dose level. For each cohort, an interim analysis will be performed prior to opening the
second stage of enrollment in each cohort (Simon's two-stage optimal design).
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. Enrollment will follow a Simon's two-stage design enrollment, similar to Phase
Ib.
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 12 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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mary Crowley Cancer Research Center
Address:
City:
Dallas
Zip:
40118
Country:
United States
Status:
Recruiting
Contact:
Last name:
Douglas Orr
Facility:
Name:
NEXT Oncology San Antonio
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ildefonso Rodriguez Rivera
Facility:
Name:
Next Oncology Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mohamad Adham Salkeni
Facility:
Name:
Summit Cancer Centers - Spokane Valley
Address:
City:
Spokane
Zip:
99208
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arvind Chaudhry
Start date:
October 9, 2023
Completion date:
October 2026
Lead sponsor:
Agency:
1ST Biotherapeutics, Inc.
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
1ST Biotherapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05761223
