To determine the maximum tolerated dose (MTD) of SAR566658
- To characterize the safety profile of SAR566658
- To evaluate the pharmacokinetic profile of SAR566658
- To assess the potential immunogenicity of SAR566658
- To assess preliminary antitumor activity
- To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using
- To assess safety in the alternative schedules of SAR566658 administration
Diagnosis of CA6-positive solid tumors as moderate to intense membrane staining of 15% of
tumor cells for which no standard therapy is available.
- Eastem Cooperative Oncology Group performance status 2.
- Any serious active disease or co-morbid condition, which, in the opinion of the
Investigator, may interfere with the safety or the compliance with the study.
- Poor bone marrow reserve.
- Poor liver and renal function.
- Pregnant or breast-feeding woman.
- No use of effective birth control methods, when applicable.
- No resolution of all specific toxicities (excluding alopecia) related to any prior
anti-cancer therapy to Grade 1 according to the National Cancer Institute - Common
Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 grade scaling.
- Wash out period of less than 3 weeks from previous antitumor therapy or any
investigational treatment, (and less than 6 weeks in case of prior nitroso-urea and
or mitomycin C treatment). Patients will be eligible if hormonotherapy (ie, for
breast tumors) is discontinued before first Investigational product administration.
- Wash out period of less than 1 week from last palliative dose of radiotherapy.
- Patients with respiratory insufficiency defined by a decrease more than 50% compared
to theoretical baseline pulmonary volumes and theoretical baseline Diffusing capacity
of the Lung for Carbon monoxyde.
- Any lung radiotherapy in patient's cancer history.
- Patients with previous history or active interstitial lung disease or pulmonary
- Patients with abnormal cardiac function defined by a Left Ventricular Ejection
- Patients with previous history of acute cardiac failure.
- Patients with previous history and/or unresolved corneal disorders.
- Known intolerance to infused protein products or maytansinoids.
- Patients treated with strong CYP3A inhibitors within 2 weeks prior study drug
- For patients to be treated in the midazolam cohort:
- Any treatment known to induce CYP3A isoenzymes or to inhibit CYP3A4 activities not
allowed within 2 weeks before midazolam administration and up to the end of
pharmacokinetic sampling following the last midazolam administration.
- Any contra-indications to midazolam, according to the applicable labeling.
- Patients older than 60 years.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Overall safety profile based on adverse events reporting, laboratory tests, vital signs and specific pulmonary and ocular tests, according to the NCI-CTC AE v4.03
Pharmacokinetic (PK) parameters
Immunogenicity evaluation (anti-drug antibodies)
To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using midazolam
To assess safety in the alternative schedules of SAR566658 administration