While TNBC patients with pCR/RCB-0 or RCB-1 have excellent survival, those with extensive residual disease (RCB-II or RCB-III) after NACT have poor prognosis. At MD Anderson, through the Moonshot Initiative, we have created a biomarker-driven drug development strategy, ARTEMIS (A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival) to identify novel targeted therapies for tumors that are predicted to be insensitive to standard NACT. Molecular profiling along with imaging is used to identify patients with chemo-insensitive disease and inform second phase of therapy incorporating targeted agents to improve responses. Folate receptor α (FRα) is a GPI-anchored surface protein encoded by FOLR1 gene that is overexpressed in multiple cancers including TNBC. Mirvetuximab soravtansine is an antibody-drug conjugate that consists of a monoclonal antibody against FRα conjugated to maytansinoid, a microtubule inhibitor. Nearly 40% of TNBC express high levels of FRα, suggesting that FRα directed therapy is a viable therapeutic strategy.
The study will include a lead in cohort (Cohort A) to establish efficacy in metastatic TNBC patients and a neoadjuvant cohort (Cohort B) to determine activity in chemo-insensitive, localized TNBC patients. If > 2 patients in Cohort A have response, the neoadjuvant cohort will be activated. Patients deemed to have chemo-insensitive, FRα+ TNBC identified through the ARTEMIS are eligible for Cohort B. The primary objectives are to determine the response rate of single agent mirvetuximab in metastatic FRa+ TNBC (> 2 lines of therapy) and to determine if mirvetuximab would improve the rates of neoadjuvant pathologic response (pCR or RCB-I) from 5% to 20% in patients with high risk, chemo-insensitive, FRa+ TNBC. A two-stage Gehan-type design with 14 patients in the first stage will be employed for the neoadjuvant cohort (n = 37). Mirvetuximab will be given IV every 21 days (6 mg/kg). Correlatives include assessment of FOLR1/FRα and characterization of biomarkers of immune modulation.
Clinical trial identification
Legal entity responsible for the study
M.D. Anderson Cancer Center
All authors have declared no conflicts of interest.