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; FORWARD II
Phase	Ib/II
Drug Class	Antibody Drug Conjugates: FRalpha
Drug Name	Mirvetuximab soravtansine
Alternate Drug Names	M9346A-sulfo-SPDB-DM4, IMGN853, Anti-FOLR1-mab Maytansinoid Conjugate
Drugs in Trial	Bevacizumab, Mirvetuximab soravtansine
Eligible Participant	Platinum resistant FRalpha+ ovarian cancer; IHC: ≥ 25% tumor cells at ≥ 2+ intensity
Patients Enrolled	94; median 3 prior therapies; 59% w/ prior bevacizumab, 27% w/ prior PARPi
Therapy Setting	Recurrence
Study Design	Open-Label, Non-randomized
Endpoints	ORR, DCR, DoR, PFS, RP2D, evaluated per RECIST
Biomarkers	FRalpha protein Exploratory: FRalpha high: IHC: ≥ 75% tumor cells at ≥ 2+ intensity; FRalpha medium: IHC: 50-74% tumor cells at ≥ 2+ intensity; FRalpha low: IHC: 25-49% tumor cells at ≥ 2+ intensity
Efficacy	RP2D: Bev 15 mg/kg + Mir 6 mg/kg q3w ORR: 44% (5CR, 36PR:, n=94) DCR: 90% (5CR, 36PR, 44SD, n=94) PFS: 8.2 months DoR: 9.7 months Exploratory analysis; FRalpha levels, prior Bev: FRalpha high (n=44): ORR: 48%; PFS: 9.7 months; DoR: 9.7 months FRalpha medium (n=39): ORR: 41%; PFS: 6.9 months; DoR: 9.7 months FRalpha low (n=11): ORR: 36%; PFS: 8.5 months; DoR: 18.5 months w/ prior Bev (n=39): ORR: 35%; PFS: 6.8 months: DoR: 9.7 months w/o prior Bev (n=55): ORR: 56%; PFS: 10.6 months; DoR: 10.4 months
Clinically Significant Adverse Events	Serious AE: one Bev-related death (intestinal perforation) Grade 3-4 AE: hypertension (15%)
Conclusion	The mirvetuximab soravtansine plus bevacizumab doublet is an active and well-tolerated regimen in patients with FRα-expressing platinum-resistant ovarian cancer. Promising activity was observed for patients regardless of level of FRα expression or prior bevacizumab
Reference	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 Gilbert L et al. Safety and efficacy 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 (2023) 170:241-247 https://pubmed.ncbi.nlm.nih.gov/36736157/

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