An Open-label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin 30 mg/m2 Given Every 3 Weeks in Subjects With Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Mesothelin+ platinum resistant ovarian cancer

65

Recurrence

Open-Label, Non-randomized

ORR, DCR, PFS, RP2D, evaluated per RECIST

Mesothelin protein

RP2D: 6.5mg/kg Ane IV and 30 mg/m2 PLD IV once every three weeks
ORR: 28% (1CR, 17PR, n=65)
PFS: 5.1 months

Exploratory analysis; mesothelin high and ≤3 prior therapies:
ORR: 42% (n=19)
DoR: 9 months
PFS: 8.5 months

Serious AE: any (33%)
Grade 3-4 AE: any (57%), nausea (38%), decreased appetite (31%), corneal disorder (29%), fatigue (29%), diarrhea (25%), decreased neutrophil count (24%), anemia (10%), decreased platelet counts (10%), decreased white blood cell counts (10%)

Promising activity in mesothelin-positive patients

Santin A et al. Safety and Activity of the Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Combination with Pegylated-Liposomal Doxorubicin in Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer. IGCS (2020) abstract 372
https://www.clearityfoundation.org/wp-content/uploads/2020/09/Anetumab-Ravtansine-and-Doxil-IGCS-2020-abstract.pdf

Santin AD et al. Safety and activity of anti-mesothelin antibody-drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study. Int J Gynecol Cancer (2023) 33(4):562-570
https://pubmed.ncbi.nlm.nih.gov/36564099/