OTL38 for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer

The Phase 3 study is to confirm the efficacy of OTL38 in combination with fluorescent light to detect additional Folate Receptor-positive (FR+) ovarian cancer lesions not detected by palpation and visualization under normal light in patients with FR+ ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

• OTL38 (Drug), also known as OTL38 for Injection: 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes
• near infrared camera imaging system (Device), also known as Near IR imaging: Infrared imaging used to excite OTL38 for fluorescence
• laparotomy (Procedure): primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Primary outcomes

• Efficacy Patient Level [30 days]: Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set)

Secondary outcomes

• Patient False Positive Rate [30 days]: False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set)

Sex: Female, ages: 18 Years to 85 Years

Inclusion Criteria:

* Female patients 18 years of age and older
* Have a primary diagnosis, or at high clinical suspicion, of primary ovarian cancer (of epithelial type), planned for primary surgical cytoreduction, interval debulking, or have recurrent ovarian cancer surgery, and:

  * Who are scheduled to undergo laparotomy for the debulking surgery OR
  * Who are scheduled to undergo laparoscopy and pre-authorized to undergo laparotomy for the debulking surgery if cancer is detected on the laparoscopy
* A negative serum pregnancy test at Screening followed by a negative urine pregnancy test on the day of surgery or day of admission for female patients of childbearing potential
* Female patients of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion
* Ability to understand the requirements of the study, provide written informed consent for participation in the study and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments

Exclusion Criteria:

* Previous exposure to OTL38
* Known FR-negative ovarian cancer
* Planned surgical debulking via laparoscopy or robotic surgery, with no intent of laparotomy.
* Patients with known ovarian cancer miliary disease determined preoperatively to be inoperable.
* Any medical condition that, in the opinion of the investigators, could potentially jeopardize the safety of the patient
* History of anaphylactic reactions
* History of allergy to any of the components of OTL38, including folic acid
* Pregnancy or positive pregnancy test
* Clinically significant abnormalities on electrocardiogram (ECG)
* Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Impaired renal function defined as eGFR< 50 mL/min/1.73m2
* Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin.
* Known Stage IV ovarian cancer with brain metastases
* Received an investigational agent in another clinical trial within 30 days prior to surgery
* Known sensitivity to fluorescent light

Participant flow

Outcome results

• Efficacy Patient Level (Primary), Number, percentage of participants: Full Analysis Set 26.9 (19.6 to 35.2)
• Patient False Positive Rate (Secondary), Number, percentage of participants: Full Analysis Set 20.2 (13.7 to 28.0)

Adverse events

Time frame: Incidence rates of treatment-emergent AEs (TEAEs), SAEs, and Adverse Device Effects (ADEs) Visit 1 (screening) through Visit 4 (28 days +/- 7 days).

Serious adverse events by term

Other adverse events by term

• Results publication: Tanyi JL, Randall LM, Chambers SK, Butler KA, Winer IS, Langstraat CL, Han ES, Vahrmeijer AL, Chon HS, Morgan MA, Powell MA, Tseng JH, Lopez AS, Wenham RM. A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006). J Clin Oncol. 2023 Jan 10;41(2):276-284. doi: 10.1200/JCO.22.00291. Epub 2022 Sep 7. PMID 36070540

• Study Protocol (PDF, 2018-11-27)
• Statistical Analysis Plan (PDF, 2017-05-16)

• Janos Tanyi, MD, Principal investigator, University of Pennsylvania