This is a first-in-human, Phase 1/2 study to evaluate LCB84, a TROP2-directed antibody-drug conjugate, alone and in combination with an anti-PD-1 Ab, in dose escalation (Phase 1) followed by dose expansion (Phase 2). The study population in dose escalation (Phase 1) consists of patients with advanced solid tumors refractory to standard of care, or for whom no standard of care exists. After the MTD and/or RP2D for single agent LCB84 is determined, dose escalation cohorts with select tumor types will be enrolled. Combination LCB84 and anti-PD-1 Ab will be evaluated in dose escalation after a minimum of 2 dose levels of single agent LCB84 have established DLT safety, to determine the MTD and/or RP2D of combination LCB84 and anti-PD-1 Ab, and to continue into dose expansion cohorts in select tumor types.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
TROP2-directed human monoclonal antibody (Ab) linked to a monomethyl auristatin E (MMAE) prodrug
anti-PD-1 Ab
Cedars Sinai Medical Center
Los Angeles, California, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
RECRUITINGTennessee Oncology
Nashville, Tennessee, United States
NOT_YET_RECRUITINGMary Crowley Cancer Research
Dallas, Texas, United States
RECRUITINGUniversity of Texas Southwestern Medical Center
Dallas, Texas, United States
NOT_YET_RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGPrincess Margaret Cancer Centre
Toronto, Ontario, Canada
RECRUITINGSafety of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1 and 2)
Incidence and severity of AEs and SAEs
Time frame: Up to 48 months
Recommended Phase 2 Dose of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1)
Based on tolerability, preliminary anti tumor activity, and pharmacokinetics
Time frame: Up to 24 months
Objective Response Rate (Phase 2)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Clinical Benefit Rate (Phase 2)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Duration of Response (Phase 2)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Time to Progression (Phase 2)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Progression Free Survival (Phase 2)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Overall Survival (Phase 2)
Survival rates
Time frame: Up to 24 months
Plasma Concentrations of LCB84 (Phase 1 and 2)
Pharmacokinetic parameters will be determined from observed concentrations of LCB84
Time frame: Up to 48 months
Evaluation of the immunogenicity of LCB84 (Phase 1 and 2)
Occurrence of ADA measured in serum at selected timepoints during the study
Time frame: Up to 48 months
Objective Response Rate (Phase 1)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Duration of Response (Phase 1)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Time to Progression (Phase 1)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
Progression Free Survival (Phase 1)
Assessed by RECIST 1.1, iRECIST, and RANO-BM
Time frame: Up to 24 months
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