Sequential multiple-assignment randomised trials to find the best order of ADCs
Patients are randomised at each decision point, not just at the start, so one trial can compare whole treatment sequences rather than single drugs.
SMART designs, standard in behavioural science, randomise patients again at progression. In metastatic breast cancer where three ADCs (T-DXd, sacituzumab, Dato-DXd) and multiple payload classes compete, a SMART would compare sequences (A then B versus B then A, payload switch versus antigen switch) with a primary endpoint of time to failure of the second line or overall survival.
- Too many combinations to test · There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
Pages like this
not linked directly; found by shared links- IdeaUse SLFN11 status to decide which antibody-drug payload to give next
Shares Sequencing HER2 ADCs by payload after T-DXd, Payload-class switching as the rule for ADC sequencing, ADC sequencing, Acquired resistance to every therapy.
- IdeaDual-payload ADCs in first line to prevent resistance
Shares Payload-class switching as the rule for ADC sequencing, Too many combinations to test, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
- IdeaA registry of every treatment sequence patients actually receive, with outcomes
Shares Registry-embedded randomisation of treatment order in routine care, ADC sequencing, Too many combinations to test.
- IdeaPatient-derived organoids to pick ADC payloads
Shares Sacituzumab govitecan, Datopotamab deruxtecan, Too many combinations to test, Antibody-drug conjugate (ADC).
- TechnologyDual-payload ADC
Shares Payload-class switching as the rule for ADC sequencing, Too many combinations to test, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
- PersonSara M. Tolaney
Shares Sacituzumab govitecan, Datopotamab deruxtecan, Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
- CompanyMersana Therapeutics
Shares ADC sequencing, Acquired resistance to every therapy, Antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC).
- PathwayDrug efflux pumps (ABC transporters)
Shares Drug efflux pumps (ABC transporters), ADC sequencing, Sacituzumab govitecan, Datopotamab deruxtecan.