{"entity":{"id":"idea-fra-adc-sequencing-ovarian","kind":"idea","name":"Sequence folate-receptor ADCs by payload class","aka":[],"tldr":"Three FRα ADCs carry different poisons (tubulin, hemiasterlin, topoisomerase). Use them in sequence rather than treating them as interchangeable.","summary":"Three folate receptor alpha antibody-drug conjugates in ovarian cancer share an antigen but not a payload: mirvetuximab soravtansine carries the tubulin agent DM4 and is used only in FRalpha-high tumours, luveltamab tazevibulin carries a hemiasterlin, and rinatabart sesutecan carries the topoisomerase 1 inhibitor exatecan. The idea is to sequence them by payload class rather than treating them as interchangeable. The rationale is that resistance to a tubulin payload, through tubulin mutations or efflux, is not expected to cross to a topoisomerase payload, and FRalpha is rarely lost at progression. The test would be a post-mirvetuximab cohort of RAINFOL-02 or a phase 2 with paired biopsies; the evidence is preclinical, and the idea connects to the general rule of payload-class switching.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04209855: MIRASOL / GOG-3045","url":"https://clinicaltrials.gov/study/NCT04209855"}],"tags":[],"related":["idea-payload-switching"],"cancers":["ovarian"],"sections":[],"technologies":[],"targets":["folr1"],"drugs":["mirvetuximab-soravtansine","rinatabart-sesutecan","luveltamab-tazevibulin"],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mirasol-nejm-2023","paper-mirvetuximab-soravtansine-ovarian-j-clin-oncol-2023","paper-mirvetuximab-soravtansine-ovarian-ann-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"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.","test":"Post-mirvetuximab cohort in RAINFOL-02 or a dedicated phase 2 with paired biopsies for FRα and payload-resistance markers.","maturity":"preclinical-evidence"},"route":"/ideas/idea-fra-adc-sequencing-ovarian/","neighbours":{"idea":[{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/"}],"cancer":[{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-resistant-ovarian-cancer","kind":"cancer","name":"Platinum-resistant ovarian cancer","route":"/cancers/platinum-resistant-ovarian-cancer/"}],"target":[{"id":"folr1","kind":"target","name":"Folate receptor alpha","route":"/targets/folr1/"}],"drug":[{"id":"luveltamab-tazevibulin","kind":"drug","name":"Luveltamab tazevibulin","route":"/drugs/luveltamab-tazevibulin/"},{"id":"mirvetuximab-soravtansine","kind":"drug","name":"Mirvetuximab soravtansine","route":"/drugs/mirvetuximab-soravtansine/"},{"id":"rinatabart-sesutecan","kind":"drug","name":"Rinatabart sesutecan","route":"/drugs/rinatabart-sesutecan/"}],"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"}],"paper":[{"id":"paper-mirvetuximab-soravtansine-ovarian-j-clin-oncol-2023","kind":"paper","name":"Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study","route":"/key-papers/paper-mirvetuximab-soravtansine-ovarian-j-clin-oncol-2023/"},{"id":"paper-mirasol-nejm-2023","kind":"paper","name":"MIRASOL: mirvetuximab soravtansine versus chemotherapy in folate receptor alpha-high platinum-resistant ovarian cancer","route":"/key-papers/paper-mirasol-nejm-2023/"},{"id":"paper-mirvetuximab-soravtansine-ovarian-ann-oncol-2021","kind":"paper","name":"Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I","route":"/key-papers/paper-mirvetuximab-soravtansine-ovarian-ann-oncol-2021/"}]}}