An open-label, Phase I study to assess the effect of itraconazole (CYP3A4 and P-gp inhibitor) on the pharmacokinetics of anetumab ravtansine and to assess the ECG effects, safety and immunogenicity of anetumab ravtansine given as a single agent and together with itraconazole in subjects with mesothelin-expressing advanced solid cancers.

DM4, the cytotoxic toxophore within anetumab ravtansine, is a substrate of
CYP3A4, and clinically significant impact of strong CYP3A4 inhibitors or
inducers on plasma concentrations of DM4 cannot be ruled out. DM4-Me (the
metabolite of DM4) is a P-gp substrate, and an impact of strong P-gp inhibitors
or inducers on plasma concentrations of DM4-Me cannot be ruled out. Therefore,
one of the purposes of the current study is to evaluate the effect of
itraconazole as strong CYP3A4 inhibitor on the safety and PK of anetumab
ravtansine.

The other purpose of the current study is to assess the ECG effects of anetumab
ravtansine given as a single agent and together with itraconazole. The
co-administration of anetumab ravtansine and itraconazole as a potent CYP3A4
inhibitor and an P-gp inhibition may result in an increase in the plasma
exposure of DM4 and DM4-Me; therefore, the current study would present an
opportune context for the *thorough* QT/QTc assessment together with the DDI
assessment.

Main objective:
- Evaluate the effect of itraconazole, a strong cytochrome P450 (CYP) 3A4
inhibitor and a P-glycoprotein (P-gp) inhibitor, on the safety and tolerability
(including "thorough" electrocardiogram [ECG] assessment) and pharmacokinetics
of anetumab ravtansine in subjects with mesothelin-expressing advanced solid
cancers.

Secondary objectives:
- Evaluate the general safety and tolerability of anetumab ravtansine in
subjects with mesothelin-expressing advanced solid cancers.
- Evaluate the multiple-dose PK of anetumab ravtansine in subjects with
mesothelin-expressing advanced solid cancers.
- Evaluate the immunogenicity of anetumab ravtansine.

This is a Phase I, multi-center, open-label, non-randomized, uncontrolled,
2-part sequential drug-drug interaction (DDI) study to assess the effect of
the CYP3A4 and P-gp inhibitor itraconazole on the PK of anetumab ravtansine and
to assess the ECG effects, safety and immunogenicity of
anetumab ravtansine given as a single agent and together with itraconazole in
subjects with advanced solid cancers.

Anetumab ravtansine given intravenous (IV) infusion over 1 hour:

On Day 1 of each 21-day treatment cycle
Part 1:
Cycle 1 Day 1: 6.5 mg/kg of body weight (BW)
Cycle 2 Day 1: 0.6 mg/kg BW

Part 2:
Cycle 1 Day 1: 6.5 mg/kg BW
Cycle 2 Day 1: 6.5 mg/kg BW (planned dose)

Continuous treatment: Cycles >=3 Day 1: 6.5 mg/kg BW once every 3 weeks (Q3W)

Itraconazole/Sporanox, 100 mg oral capsules given by mouth:

Part 1 + 2:
Cycle 1
(Day 18): 200 mg twice daily (BID)
(Days 19 - 21): 200 mg once daily (QD)

Cycle 2 (Days 1-8) 200 mg QD
12 days in total (part 1 and 2)

Treatment with anetumab ravtansine may have some therapeutic benefit but this
cannot be guaranteed.

Most common risks of anetumab ravtansine are nausea, fatigue, vomiting,
anorexia, diarrhea, peripheral neuropathy, increased ALT and AST and eye
toxicity.

Participation in the study involves daily/ weekly / three weekly visits with
blood tests and physical exams. Blood samples for PK analysis will be taken 14
times during first 3 cycles (9 of them - at Day 1 of each cycle). Continuous
(Holter) ECG monitoring lasting 11 hours will be done 5 times during the first
3 treatment cycles. Visits will continue until the disease progression or
intolerable toxicity, further follow up will be done for one more until 1 month.

Examinations including eye examination, ECG and tumor assessments will be
performed at specific visits.