This is a Phase Ib/II, open-label, multi-cohort, multi-center study to evaluate the safety, tolerability, and preliminary anti-tumor activity of GB268, a biological product, as monotherapy or in combination with other therapies in patients with locally advanced unresectable or metastatic breast cancer.
The Phase Ib part of the study will primarily assess the safety and tolerability of GB268 in combination therapies, including dose-limiting toxicities (DLTs). The Phase II part will primarily evaluate the preliminary anti-tumor activity of GB268 as monotherapy and in various combination regimens in corresponding breast cancer populations.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
270
GB268 is a tri-specific antibody targeting PD-1, CTLA-4, and VEGF. It is designed to block immune checkpoints (PD-1/CTLA-4) to enhance T-cell-mediated anti-tumor immune responses and simultaneously inhibit VEGF-mediated tumor angiogenesis
Nab-Paclitaxel is a microtubule-stabilizing agent formulated as albumin-bound nanoparticles for IV administration.
Datopotamab Deruxtecan is an ADC targeting Trop-2, consisting of a monoclonal antibody linked to a topoisomerase I inhibitor payload.
Dose-Limiting Toxicities [DLTs] (Phase Ib)
Incidence of Dose-Limiting Toxicities \[DLTs\] during the first treatment cycle
Time frame: Within 21 days after first dose
Objective Response Rate [ORR] (Phase II)
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on Investigator per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]
Time frame: Up to approximately 2 years
Number of participants with adverse events [AEs] (Phase Ib and Phase II)
Safety as assessed by clinical laboratory tests, 12-lead electrocardiogram (ECG), vital signs measurements, and the incidence, nature and severity of all adverse events (AEs) and serious AEs (SAEs)
Time frame: Up to approximately 2 years
Objective Response Rate [ORR] (Phase Ib)
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.
Time frame: Up to approximately 2 years
Duration of Response [DOR] (Phase Ib and Phase II)
DOR assessed according to RECIST v1.1
Time frame: Up to approximately 2 years
Overall Survival [OS] (Phase Ib and Phase II)
OS defined as the time from the first dose to death from any cause
Time frame: Up to approximately 2 years
Disease Control Rate [DCR] (Phase Ib and Phase II)
DCR assessed according to RECIST v1.1
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A Trop-2-directed Antibody-Drug Conjugate \[ADC\] consisting of a humanized anti-Trop-2 monoclonal antibody covalently linked to a topoisomerase I inhibitor payload.
Time frame: Up to approximately 2 years
Progression-Free Survival [PFS] (Phase Ib and Phase II)
PFS assessed according to RECIST v1.1
Time frame: Up to approximately 2 years
Cmax of GB268 of GB268 (Phase Ib and Phase II)
Peak plasma concentration
Time frame: Up to approximately 2 years
Tmax of GB268 (Phase Ib and Phase II)
Time to peak drug concentration
Time frame: Up to approximately 2 years
AUC of GB268 (Phase Ib and Phase II)
Area under curve
Time frame: Up to approximately 2 years
Number and percentage of participants with Anti-Drug Antibodies [ADAs] (Phase Ib and Phase II)
Time frame: Up to approximately 2 years