T-cell Therapy in Combination With Nivolumab, Relatlimab and Ipilimumab for Patients With Metastatic Ovarian Cancer

Peritoneal Cancer Clinical Trial

Official title: T-cell Therapy in Combination With Nivolumab, Relatlimab and Ipilimumab for Patients With Advanced Ovarian-, Fallopian Tube- and Primary Peritoneal Cancer

Status Recruiting

Clinical Trial Summary

Although immunotherapy has revolutionized the treatment of many cancers, ovarian cancer patients have not yet benefitted from the advances.

In two consecutive pilot trials at National Center for Cancer Immune Therapy (CCIT-DK), is has been have shown that adoptive cell therapy (ACT) with TILs for patients with advanced ovarian cancer (OC) is feasible and tolerable. In the most recent of these trials ACT was combined with a CTLA-4 inhibitor, Ipilimumab and a PD1-inhibitor, Nivolumab. Only transient clinical responses where observed.

Between 90-100 % of infused T-cells in our previous ovarian cancer ACT trial expressed LAG-3. The interaction between LAG-3 on T-cells and MHC-II on tumor cells inhibits T-cell function.

In this study adding the LAG-3 antibody Relatlimab to the ACT-regimen described above may therefore well unleash T-cell antitumor efficacy by blocking the known LAG-3-MHC-II interaction.

With this study the aim is to demonstrate that adding the lag-3-inhibitor Relatlimab to the above treatment regimen is feasible and tolerable. The study will elucidate whether the combination Relatlimab-Nivolumab leads to objective responses and improves progression free survival (PFS).

Clinical Trial Description

Rationale T-cell therapy is an experimental personalized immunotherapy where TILs are isolated from the patient's own tumor tissue, expanded in vitro to billions of cells and then administered to the individual patient with the purpose of eliminating the remaining cancer cells. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine phosphate is administered to the patient before TIL infusion to reduce the number of irrelevant immune cells.

In two consecutive pilot trials at National Center for Cancer Immune Therapy (CCIT-DK), it has been shown that adoptive cell therapy (ACT) with TILs for patients with advanced ovarian cancer (OC) is feasible and tolerable. In the most recent of these trials ACT was combined with a CTLA-4 inhibitor, Ipilimumab and a PD1-inhibitor, Nivolumab.

Between 90-100% of infused T-cells in these previous ovarian cancer ACT trial expressed LAG-3. The interaction between LAG-3 on T-cells and MHC-II on tumor cells inhibits T-cell function.

In this phase I/II study 18 patients with advanced ovarian -, fallopian tube-, and primary peritoneal cancer will be included. Included patients undergo surgical removal of tumor tissue for tumor-infiltrating lymphocyte (TIL) manufacturing. Lymphodepleting chemotherapy is administered prior to TIL infusion. Hereafter the patients are treated with the programmed cell death protein 1 (PD-1) antibody Nivolumab and the anti-lymphocyte activation gene 3 (anti-LAG-3) antibody Relatlimab. The study will be devided into 3 steps.

• Step One (6 subjects): Patients are treated without prior administration of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody Ipilimumab pre-tumor harvest.

• Step Two (6 subjects): If Step One proves feasible and tolerable patients in Step Two will receive one dose of Ipilimumab pre-tumor harvest.

• Step Three (6 subjects): Patients are treated either with or without prior Ipilimumab pre-tumor harvest depending on the tolerability data from Step Two.

All patients are treated with lymphodepleting chemotherapy for 7 days followed by infusion of TILs. For safety reasons no IL-2- will be administered in this study

The aim of this study is to demonstrate that ACT and a combination of Relatlimab-Nivolumab does not increase the toxicity compared to the same treatment regimen including Nivolumab monotherapy. The study will elucidate whether the combination Relatlimab-Nivolumab lead to objective responses and improves progression free survival (PFS). It is anticipated that combining Relatlimab and Nivolumab with Adoptive T cell therapy (ACT) for advanced OC is safe and feasible. Further, it is hypothesized that the combination will lead to improved immunity in tumor and blood as well as improved antitumor efficacy.

Objectives

• To evaluate the tolerability and safety of the treatment

• To characterize antitumor immune responses and clinical efficacy ;

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• Metastatic Fallopian Tube Cancer
• Metastatic Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cancer

• NCT number: NCT04611126
• Study type: Interventional
• Source: Herlev Hospital
• Contact: Inge Marie Svane, Prof, M.D.
• Phone: +4538683868
• Email: inge.marie.svane@regionh.dk
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 22, 2021
• Completion date: December 2023