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

Trial ID # NCT02606305
Phase Ib/II
Drug Class Angiogenesis Inhibitors: VEGF
Drug Name Bevacizumab
Alternate Drug Names immunoglobulin G1 (human-mouse monoclonal rhuMab-VEGF gamma-chain, anti-VEGF monoclonal antibody, Avastin
Drugs in Trial Bevacizumab, Mirvetuximab Soravtansine
Eligible Participant

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

Patients Enrolled

66; median 3 prior therapies (1-8)

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, DoR, PFS, RP2D, evaluated per RECIST

Biomarkers

FRalpha protein

Efficacy

RP2D: Bev 15 mg/kg + Mir 6 mg/kg q3w
ORR: 39% (5CR, 21PR, n=66)
PFS: 6.9 months (4.9-8.6)
DoR: 8.6 months (4.9-14.9)

Exploratory analysis FORWARD I criteria (≥ 50% of tumor cells with ≥ 2+ FRalpha expression, ≤3 previous therapies):
ORR: 48% (1CR, 10PR, n=23)
PFS: 9.9 months (4.6-14.5)
DoR: 10.6 months (3.3-12.0)

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

Clinically Significant Adverse Events

Serious AE: one Bev-related death (intestinal perforation)
Grade 3-4 AE: hypertension (14%)

Conclusion

Encouraging activity in FRalpha-positive patients

Reference

O’Malley DM et al. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Final findings from the FORWARD II study. J Clin Oncol (2019) 37 (suppl; abstr 5520)
https://meetinglibrary.asco.org/record/176009/abstract

O’Malley DM et al. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination withbevacizumab in patients (pts) with platinum-resistant ovarian cancer:Maturing safety and activity profile from the FORWARD II phase 1b study. J Clin Oncol (2018) 36 (suppl; abstr 5549)
https://meetinglibrary.asco.org/record/162345/abstract