A Phase I Dose-Escalation Safety and Tolerability Study of MirvetuximabSoravtansine (IMGN853) and Gemcitabine in Patients With FRa-positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial Cancer, or Triple Negative Breast Cancer (TNBC)

FRalpha+ recurrent ovarian, endometrial or triple negative breast cancer with IHC: ≥ 25% tumor cells at ≥ 2+ intensity

22 ovarian treated at RP2D, median 3 prior therapies (3-4), 56% w/ prior bevacizumab, 59% w/ prior PARP inhibitor

Recurrence

Open-Label, Non-randomized

ORR, DCR, PFS, RP2D, evaluated per RECIST

RP2D: 6mg/kg mirvetuximab soravtansine q3w and 800mg/m2 gemcitabine days 1 and 8 q3w
Patients dosed at RP2D: 3 low FRalpha+ (IHC: 25-50% at ≥ 2+ intensity), 7 medium FRalpha+ (IHC: 50-75% at ≥ 2+ intensity), 12 high FRalpha+ (IHC: 75-100% at ≥ 2+ intensity)

ORR: 40.9% (9PR, n=22)
DCR: 86.4% (9PR, 10SD, n=22)
PFS: 7.5 months

Serious AE:
Grade 3-4 AE: anemia (11%), decreased lymphocyte counts (16%), decreased neutrophil counts (26%), decreased platelet counts (11%), decreased white cell counts (16%), fatigue (115)

Mirvetuximab soravtansine and gemcitabine demonstrate promising activity in platinum resistant ovarian cancer, but with frequent hematologic toxicities

Cristea MC et al. A phase I study of mirvetuximab soravtansine (MIRV) and gemcitabine (G) in patients (Pts) with selected frα-positive solid tumors: Results in the ovarian cancer (EC) cohort. J Clin Oncol (2021) 39 (suppl 15; abstr 5542)
https://meetinglibrary.asco.org/record/197431/abstract

Cristea MC et al. Poster
https://www.clearityfoundation.org/wp-content/uploads/2021/06/MirvetuximabGemzar-poster-ASCO-2021-scaled.jpeg

Cristea MC et al. A phase I study of Mirvetuximab Soravtansine and gemcitabine in patients with FRα-positive recurrent ovarian, primary peritoneal, fallopian tube, or endometrial cancer, or triple negative breast cancer. Gynecol Oncol (2024) 182:124-131
https://pubmed.ncbi.nlm.nih.gov/38262235/