Study for Intra-operative Imaging of Cancer using a New Fluorescent Agent

It is important to improve visualization of tumors and metastases, such as in ovarian, renal cell and endometrial cancer, in real time during surgery to enable the surgeon to excise more of the tumor, and also to facilitate proper staging. Intra-operative identification of cancer tissue using new real-time imaging modalities that could provide clear tumor identification and demarcation would provide a very useful tool to reduce positive resection margins and increase full removal of the tumor hence reducing rates of re-interventions and therefore may reduce morbidity and improve patient outcome. Furthermore, if otherwise invisible tumor lesions and metastasis can be identified, tumor staging will be possibly improved which influences treatment choices. In the last few years, a novel optical imaging platform has emerged. The use of fluorescent probes that recognize cancer-specific antigens, in conjunction with a clinical imaging system, are under investigation. OTL38, a fluorescent probe that targets the folate receptor alpha (FRa), a receptor over-expressed in most ovarian, renal and serous and clear cell endometrial cancers, and that emits lights with wavelengths in the near-infrared (NIR) spectrum, along with an imaging system, can be used to visualize FRa positive cancer in patients during surgery. This could enable the surgeon to excise more of the tumor tissue as compared to usual visual and tactile methods.

1. To assess the safety and tolerability of different doses of a single IV injection of OTL-038

2. To assess the efficacy of ascending doses of a single IV injection of OTL-038 in detecting ovarian, renal cell or endometrial cancer during surgery by :

a. Tumor to background ratio (TBR)

b. Concordance between fluorescent signal and tumor status of resected tissue

c. Detection of more FR-a+, cancer+ tumor lesions or resection margins with fluorescent light compared to usual visual/tactile conditions

3. To assess the surgeons’ opinion regarding the utility of OTL-038 IV injection and imaging system in debulking or staging of ovarian cancer or endometrial cancer or surgical removal of renal cell cancer

4. To assess the pharmacokinetics of ascending doses of a single IV injection of OTL-038

Visit 1 (Screening, up to Day -60)

Provide written informed consent; complete medical history and physical examination; vital signs and weight; ECG tracing; clinical hematology and chemistry laboratory assessments; blood pregnancy test for females of child-bearing potential; and collection of concomitant medication information



Visit 2 (Day of surgery)

A single dose of OTL-038 will be administered IV over 60 minutes to each subject two to three hours prior to surgery.
Blood samples for assessment of OTL-038 PK will be taken at time points specified in the schedule of assessments. Planned surgery will be performed during which real-time imaging of the lesions utilizing a fluorescent imaging system will be done.



Visit 2 (After surgery, admission day Day 2)

Routine-post surgical follow-up with dedicated assessment of any AEs up to 24 hours will occur. Patients will be hospitalized post-operatively per routine standard of care and blood samples for routine analyses will be taken as part of standard of care. And at 24 hours post dosing a last PK sample will be obtained.

Visit 3 (Follow up)

Telephonic follow up with dedicated assessment of AEs and concomitant medication.

Single IV injection of OTL38 at doses of 0.0125, 0.025, 0.05 and 0.1mg/kg bodyweight