OnCo
ideasIdea

Sequence folate-receptor ADCs by payload class

Three FRα ADCs carry different poisons (tubulin, hemiasterlin, topoisomerase). Use them in sequence rather than treating them as interchangeable.

Mirvetuximab (DM4, FRα-high only), luveltamab tazevibulin (hemiasterlin, any FRα), and Rina-S (exatecan, any FRα) share the antigen but not the payload. Cross-resistance between tubulin and TOP1 payloads is expected to be low, and FRα is rarely lost at progression.

Hypothesis
Patients progressing on mirvetuximab retain FRα and respond to a TOP1-payload FRα ADC at rates similar to ADC-naive patients.
Rationale
Payload-specific resistance (tubulin mutations, efflux) does not cross to topoisomerase payloads; FRα PET or repeat biopsy can confirm antigen persistence.
What would test it
Post-mirvetuximab cohort in RAINFOL-02 or a dedicated phase 2 with paired biopsies for FRα and payload-resistance markers.
Maturity
preclinical evidence

Connected

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cancers

1
Ovarian cancer

targets

1
Folate receptor alpha

drugs

3
Phase 3ADC
Luveltamab tazevibulin
ApprovedADC
Mirvetuximab soravtansine · Elahere
Phase 3ADC
Rinatabart sesutecan

terms

1
ADC sequencing

ideas

1
Payload-class switching as the rule for ADC sequencing