To evaluate the clinical efficacy (objective response rate, ORR) of mass spectrometry-based absolute quantification-guided selection and matching of ADC/PDC therapy in patients with locally advanced or metastatic pancreatic cancer/breast cancer, and to explore a quantitative threshold-based stratification strategy for identifying a "hidden benefit population
This is a single-center, open-label, single-arm, umbrella clinical trial comprising dual cohorts for pancreatic cancer and breast cancer, with multiple sub-cohorts within each cohort. A Bayesian optimal two-stage design will be employed for dynamic decision-making. The study consists of a screening period, a treatment period, and a follow-up period. Two cohorts are established: the Pancreatic Cancer cohort (PC) and the Breast Cancer cohort (BC). During the screening period, all enrolled patients will provide fresh or archived tumor tissue for absolute quantification of membrane proteins via a mass spectrometry platform, generating an individualized "target expression profile" (expressed as molecules per cell). Targets will be ranked by expression level in descending order to identify the top 1-5 candidate targets.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
225
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) consisting of the humanized anti-HER2 monoclonal antibody trastuzumab covalently linked to the cytotoxic maytansinoid DM1 via a non-cleavable thioether linker (SMCC). T-DM1 is administered intravenously at a dose of 3.6 mg/kg every 3 weeks (Q3W).
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) consisting of the humanized anti-HER2 monoclonal antibody trastuzumab covalently linked to the topoisomerase I inhibitor payload DXd via a cleavable tetrapeptide-based linker (GGFG). T-DXd is administered intravenously at a dose of 5.4 mg/kg every 3 weeks (Q3W).
Fudan University Shanghai Cancer Cancer
Shanghai, Shanghai Municipality, China
Objective Response Rate (ORR) as Assessed by RECIST 1.1
ORR is defined as the proportion of participants achieving a best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 criteria, as assessed by the investigator.
Time frame: Up to 104 Weeks
Disease Control Rate (DCR) as Assessed by RECIST 1.1
Disease Control Rate (DCR), defined as the proportion of patients achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed by RECIST 1.1.
Time frame: Up to 104 Weeks
Duration of Response (DoR)
DoR is defined as the time from the first documented response (CR or PR) to the first documented disease progression or death from any cause, as assessed by RECIST 1.1.
Time frame: Up to 104 Weeks
Progression-Free Survival (PFS)
Progression-Free Survival (PFS), defined as the time from the start of treatment to the first documented disease progression or death from any cause, whichever occurs first, as assessed by RECIST 1.1.
Time frame: Up to 104 Weeks
Overall Survival (OS)
Overall Survival (OS), defined as the time from the start of treatment to death from any cause.
Time frame: Up to 104 Weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to the topoisomerase I inhibitor payload DXd via a cleavable tetrapeptide-based linker (GGFG). Dato-DXd is administered intravenously at a dose of 6 mg/kg every 3 weeks (Q3W).
Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to the topoisomerase I inhibitor payload SN-38 via a cleavable pH-sensitive carbonate linker (CL2A). SG is administered intravenously at a dose of 10 mg/kg on Days 1 and 8 of each 21-day cycle.
Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) consisting of a humanized anti-Nectin-4 IgG1 monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable protease-sensitive linker (vc, valine-citrulline). EV is administered intravenously at a dose of 1.25 mg/kg on Days 1, 8, and 15 of each 28-day cycle.
Becotatug vedotin (MRG003) is an antibody-drug conjugate (ADC) consisting of a humanized anti-EGFR IgG1 monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable protease-sensitive linker (vc, valine-citrulline). MRG003 is administered intravenously every 3 weeks (Q3W).
Izalontamab brengitecan (iza-bren; BL-B01D1) is a bispecific antibody-drug conjugate (ADC) targeting both EGFR and HER3, covalently linked to a topoisomerase I inhibitor payload. BL-B01D1 is administered intravenously.
Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate (ADC) consisting of the humanized anti-FRα monoclonal antibody M9346A covalently linked to the cytotoxic maytansinoid DM4 via a cleavable disulfide linker. MIRV is administered intravenously at a dose of 6 mg/kg adjusted ideal body weight (AIBW) on Day 1 of every 3-week cycle (Q3W).