# Sequence folate-receptor ADCs by payload class

Source: https://onco.cc/ideas/idea-fra-adc-sequencing-ovarian/  
OnCo record `idea-fra-adc-sequencing-ovarian` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- 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.
- Proposed test: Post-mirvetuximab cohort in RAINFOL-02 or a dedicated phase 2 with paired biopsies for FRα and payload-resistance markers.
- Maturity: preclinical-evidence

## Sources

- ClinicalTrials.gov NCT04209855: MIRASOL / GOG-3045: https://clinicaltrials.gov/study/NCT04209855

## Connected records

- ideas: [Payload-class switching as the rule for ADC sequencing](https://onco.cc/ideas/idea-payload-switching/)
- cancers: [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Platinum-resistant ovarian cancer](https://onco.cc/cancers/platinum-resistant-ovarian-cancer/)
- targets: [Folate receptor alpha](https://onco.cc/targets/folr1/)
- drugs: [Luveltamab tazevibulin](https://onco.cc/drugs/luveltamab-tazevibulin/), [Mirvetuximab soravtansine](https://onco.cc/drugs/mirvetuximab-soravtansine/), [Rinatabart sesutecan](https://onco.cc/drugs/rinatabart-sesutecan/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/)
- key papers: [Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study](https://onco.cc/key-papers/paper-mirvetuximab-soravtansine-ovarian-j-clin-oncol-2023/), [MIRASOL: mirvetuximab soravtansine versus chemotherapy in folate receptor alpha-high platinum-resistant ovarian cancer](https://onco.cc/key-papers/paper-mirasol-nejm-2023/), [Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I](https://onco.cc/key-papers/paper-mirvetuximab-soravtansine-ovarian-ann-oncol-2021/)

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