A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

Platinum resistant FRalpha+ ovarian cancer; IHC: ≥ 25% tumor cells at ≥ 2+ intensity

200 [Mir+Bev: 66; median 3 prior therapies (1-8); Mir+PLD: 16; median 2 prior therapies (1-6); Mir+Pem: 56; median 3 prior therapies (2-7)]

Recurrence

Open-Label, Non-randomized

ORR, PFS, RP2D, evaluated per RECIST

FRalpha protein

Mir+Bev: ORR: 39% (5CR, 21PR, n=66); PFS: 6.9 months (4.9-8.6)
Mir+PLD: ORR: 13% (n=16); PFS: 7.0 months (1.7-NR)
Mir+Pem: ORR: 30% (n=54); PFS: 4.2 months (2.8-5.9)

Exploratory analysis; medium/high FRalpha: ≥ 50% of tumor cells with ≥ 2+ FRalpha expression:
Mir+Pem (n=39): ORR: 31%; DoR: 8.1 months (4.2-NR); PFS: 5.5 months (2.8-6.3)

Exploratory analysis FORWARD I criteria (Pt-R, ≤3 previous therapies, ≥ 50% of tumor cells with ≥ 2+ FRalpha expression):
Mir+Bev: ORR: 48% (1CR, 10PR, n=23); PFS: 9.9 months (4.6-14.5)

Exploratory analysis: ≥ 50% of tumor cells with ≥ 2+ FRalpha expression and AURELIA MATCHED (bevacizumab-naive, 1-2 prior therapies) (n=16):
Mir+Bev: ORR: 56%
PFS: 9.9 months (4.1-15.9)
DoR: 12.0 months (6.0-14.9)

Mir+Bev:
Serious AE: one Bev-related death (intestinal perforation)
Grade 3-4 AE: hypertension(14%)
Mir+PLD:
Serious AE: none
Grade 3-4 AE: anemia (13%), vomiting (13%)
Mir+Pem:
Serious AE: one treatment-related death (encephalitis)
Grade 3-4 AE: overall (45%)

Encouraging activity in FRalpha+ patients

O’Malley DM et al. Safety findings from FORWARD II: A Phase 1b study evaluating the folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin (PLD), or pembrolizumab in patients (pts) with ovarian cancer. J Clin Oncol (2017) 35 (suppl; abstr 5553)
https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.5553

Matulonis UA et al. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), with pembrolizumab in platinum-resistant ovarian cancer (PROC): Initial results of an expansion cohort from FORWARD II, a Phase Ib study. Ann Oncol (2018) 29 Suppl_8, Abstract 949P, Poster
https://www.immunogen.com/wp-content/uploads/2018/10/ESMO-2018-PEMBRO-Poster-FINAL-compressed.pdf

O'Malley DM et al. Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer.  Gynecol Oncol (2020) 157(2): 379-385
https://www.ncbi.nlm.nih.gov/pubmed/32081463