NCT03287674

TIL Therapy in Combination With Checkpoint Inhibitors for Metastatic Ovarian Cancer

T-cell Therapy in Combination With Checkpoint Inhibitors for Patients With Advanced Ovarian-, Fallopian Tube- and Primary Peritoneal Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Inge Marie Svane · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo. The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.

Detailed description

Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo. The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect. Objectives: To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with ACT with TILs in combination with checkpoint inhibitors. To evaluate treatment related immune responses To evaluate clinical efficacy Design: Patients will be screened with a physical exam, medical history, blood samples and ECG. Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2 patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase the activity of the infused TIL product. On day 0 patients receive TIL infusion and shortly after starts IL-2 stimulation with a daily subcutaneous dose for a total of 14 days.The patients will followed until progression or up to 5 years.

Conditions

• Metastatic Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
DRUG	Fludarabine	Fludarabine 25 mg/m2 is administered on day -5 to day -1.
BIOLOGICAL	TIL infusion	The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
DRUG	Interleukin-2	Interleukin-2 is administered as a daily low-dose subcutaneous injection of 2 MIU for a total of 14 days.
DRUG	Ipilimumab	One dose of Ipilimumab 3 mg/kg is administered 14 days prior to surgical removal of tumor tissue for TIL expansion.
DRUG	Nivolumab	Nivolumab 3 mg/kg is administered on day -2 before TIL infusion and every 2 weeks for a total of 4 doses.

Timeline

• Start date: 2017-10-09
• Primary completion: 2020-06-01
• Completion: 2020-06-01
• First posted: 2017-09-19
• Last updated: 2023-03-01
• Results posted: 2021-03-22

Locations

1 site across 1 country: Denmark