Combination baskets defined by resistance mechanism rather than by cancer type
Group patients by why their last drug stopped working, then test the combination designed to fix that specific failure, whatever the cancer.
Progression biopsies and ctDNA now reveal resistance mechanisms (SLFN11 loss for topoisomerase-1 payloads, MET amplification for EGFR inhibitors, RB loss for CDK4/6 inhibitors). A basket trial enrolling by mechanism would test the matched rescue combination (for example ATR inhibitor plus the same ADC for SLFN11-low tumours) across histologies, converting a resistance hypothesis into a trial in months.
- 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- 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).
- 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).
- IdeaTime immunotherapy to the moment targeted drugs make tumours visible
Shares CDK4/6 inhibitors, Too many combinations to test, Acquired resistance to every therapy.
- IdeaUse SLFN11 status to decide which antibody-drug payload to give next
Shares Payload-class switching as the rule for ADC sequencing, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
- PairingCaution: TOP1 ADC immediately after TOP1 ADC
Shares Sequential multiple-assignment randomised trials to find the best order of ADCs, Payload-class switching as the rule for ADC sequencing.
- IdeaRotate between drugs on a fixed schedule instead of waiting for failure
Shares Too many combinations to test, Acquired resistance to every therapy.
- IdeaA fast route to the matched drug when it is licensed for another cancer
Shares Tumour-agnostic (tissue-agnostic) approval, Acquired resistance to every therapy.
- TermT030 (belotecan derivative)
Shares Drug efflux pumps (ABC transporters), Antibody-drug conjugate (ADC).