An Open Label Phase I Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose of the Anti-mesothelin Antibody Drug Conjugate BAY94-9343 in Subjects With Advanced Solid Tumors

Trial ID #	NCT01439152
Phase	I
Drug Class	Antibody Drug Conjugates: Mesothelin
Drug Name	Anetumab ravtansine
Alternate Drug Names	Anti-mesothelin Antibody-Drug Conjugate BAY 94-9343, BAY 94-9343
Drugs in Trial	Anetumab ravtansine
Eligible Participant	Advanced solid tumors (ovarian: platinum-resistant or partially platinum-sensitive ovarian cancer patients)
Patients Enrolled	148 (61 ovarian)
Therapy Setting	Recurrence
Study Design	Open-Label, Non-randomized
Endpoints	ORR, DCR, PFS, RP2D, evaluated per RECIST
Efficacy	RP2D: 6.5 mg/kg q3w or 2.2 mg/kg qw 21 ovarian at 6.5 mg/kg q3w: ORR: 4.8% (1PR, n=21) DCR: 57.1% (1PR, 11SD, n=21) PFS: 4.1 months 21 ovarian at 2.2 mg/kg qw: ORR: 9.5% (1CR, 1PR, n=21) DCR: 66.7% (1CR, 1PR, 12SD, n=21) PFS: 2.8 months Exploratory analysis, mesothelin expression: % viable cells with mesothelin membrane staining intensity (IHC) of 2+ or 3+: <33 (n=4) vs ≥33 to ≤66 (n=12) vs >66 (n=39): ORR: 0 vs 0 vs 12.8% DCR: 100 vs 58.3 vs 46.2%
Clinically Significant Adverse Events	Serious AE: any (11%) Grade 3-4 AE: any (29%), fatigue (16%), headache (11%)
Conclusion	Anetumab ravtansine shows preliminary activity and reversible adverse events, particularly in mesothelin+ patients
Reference	Hassan R et al. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody-Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. J Clin Oncol (2020) 38(16): 1824-1835 https://www.ncbi.nlm.nih.gov/pubmed/32213105