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 Immunotherapy: Checkpoint Inhibitors/PD-1
Drug Name Pembrolizumab
Alternate Drug Names MK3475, SCH 900475, Lambrolizumab, Keytruda
Drugs in Trial Mirvetuximab Soravtansine, Pembrolizumab
Eligible Participant

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

Patients Enrolled

56; median 3 prior therapies (2-7)

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, PFS, RP2D, evaluated per RECIST

Biomarkers

FRalpha protein

Efficacy

RP2D: Pem 200mg + Mir 6mg/kg q3w
ORR: 30% (n=54)
DoR: 6.9 months (4.2-8.3)
PFS: 4.2 months (2.8-5.9)

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

Clinically Significant Adverse Events

Serious AE: one treatment-related death (encephalitis)
Grade 3-4 AE: overall (45%)

Conclusion

Encouraging activity in FRalpha-positive patients

Reference

Matulonis UA et al. Initial safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (Frα)-targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in platinum-resistant epithelial ovarian cancer patients. SGO (2018) Abstract 74
https://www.sgo.org/wp-content/uploads/2018/03/Abstracts-2018-SGO-Annual-Meeting-on-Womens-Cancer-1.pdf

Matulonis UA et al. Mirvetuximab soravtansine, a folate receptor alpha (Frα)-targeting antibody-drug conjugate (ADC), with pembrolizumab in platinum-resistant ovariancancer (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