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

Sponsor
Inge Marie Svane
Study ID
NCT04611126
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

  • Metastatic Fallopian Tube Cancer
  • Metastatic Ovarian Cancer
  • Peritoneal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Ipilimumab — DRUG
    Ipilimumab 3 mg/kg is administered 2-6 weeks before surgical removement of the tumor. The medicine is administered i.v. over 30 minutes.
  • Cyclophosphamid — DRUG
    Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
  • Fludarabine Phosphate — DRUG
    Fludarabine 25 mg/m2 is administered on day -5 to day -1.
  • Tumor Infiltrating Lymphocytes infusion — BIOLOGICAL
    Tumor-infiltrating lymphocytes grown ex-vivo from resected from cancer tissue and reapplied to the patient via an intravenous infusion. The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
  • Nivolumab — DRUG
    Nivolumab 240 mg i.v. is administered on day -2 and every 2 weeks for a total of 4 doses. The medicine is administered over 30 minutes.
  • Relatlimab — DRUG
    Relatlimab 80 mg i.v. is administered on day -2 and every 2 weeks for a total of 4 doses. The medicine is administered over 60 minutes.

Study Details

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).

Key Dates

Start date
Apr 22, 2021
Status verified
Aug 2025
Primary completion
Mar 3, 2024
Completion
Mar 3, 2024

Study Design

Enrollment
6 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Other: Without Ipilimumab
    At Step 1, 6 patients will be treated without Ipilimumab pre tumor harvest. If feasible and tolerable, as defined by no additional SAE/SAR compared to the previously completed pilot studies at CCIT-DK, the trial will move to Step 2. Depending on the safety and feasibility on step 2, 6 more patients can be included at step 1.
  • Other: With Ipilimumab
    At Step 2, 6 patients will be included. Ipilimumab 3 mg/kg will be administered 2-6 weeks pre tumor harvest. If no additional SAE/SAR compared to the previous completed pilot study at CCIT-DK is observed additional 6 patients can be included at Step 2. If on the other hand Step 2is not found safe additional 6 patients can be included at Step 1

Primary Outcome Measure

Number of Patients Excluded Due to Treatment Related Safety Issues [ Time Frame: Until completion of the study for ]

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