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

NCT04611126 | Terminated Phase 1 Results DMC

• 1 other identifier: GY2028
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Metastatic Ovarian Cancer; Metastatic Fallopian Tube Cancer; Peritoneal Cancer

Keywords

Adoptive Cell Therapy; Immune Therapy; Tumor Infiltrating Lymphocytes

Outcome Measures

Primary Outcomes (3)

• Number of Patients Excluded Due to Treatment Related Safety Issues

  Number of patients excluded due to treatment related safety issues compared to the number of patients enrolled in the study

  Until completion of the study for

• Number of Participants Experiencing Grade III or Worse Adverse Events

  The number of Participants Experiencing Grade III or Worse Adverse Events

  Until completion of the study

• Number of Patients Excluded Due to Feasibility Issues

  Number of patients excluded due to feasibility issues compared to the number of patients enrolled in the study

  Until completion of the study

Secondary Outcomes (1)

• Best Overall Response (BOR)

  The patients were evaluated every 6-12 weeks after therapy and until study completion

Study Arms (2)

Without Ipilimumab

OTHER

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.

Drug: Cyclophosphamid; Drug: Fludarabine Phosphate; Biological: Tumor Infiltrating Lymphocytes infusion; Drug: Nivolumab; Drug: Relatlimab

With Ipilimumab

OTHER

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

Drug: Ipilimumab; Drug: Cyclophosphamid; Drug: Fludarabine Phosphate; Biological: Tumor Infiltrating Lymphocytes infusion; Drug: Nivolumab; Drug: Relatlimab

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.

With Ipilimumab

Cyclophosphamid DRUG

Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.

Also known as: Cyclophosphamide

With Ipilimumab; Without Ipilimumab

Fludarabine Phosphate DRUG

Fludarabine 25 mg/m2 is administered on day -5 to day -1.

With Ipilimumab; Without Ipilimumab

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.

Also known as: TILs

With Ipilimumab; Without Ipilimumab

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.

With Ipilimumab; Without Ipilimumab

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.

Also known as: Relalimab

With Ipilimumab; Without Ipilimumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological proven advanced ovarian-, fallopian tube or primary peritoneal cancer with the possibility of surgical removal of tumor tissue of \> 1 cm3. All histologies can be included.
• Progressive or recurrent resistant disease after platin-based chemotherapy (platinum resistant) or progressive or recurrent disease after second line or additional chemotherapy.
• Age: 18 - 75 years.
• ECOG performance status of ≤1 (Appendix 2).
• Life expectancy of \> 6 months.
• At least one measurable parameter in accordance with RECIST 1.1 -criteria.
• LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test) within 6 months from first study drug administration
• No significant toxicities or side effects (CTC ≤ 1) from previous treatments, except sensory- and motoric neuropathy (CTC ≤ 2) and/or alopecia (CTC ≤ 2).
• Sufficient organ function, including:
• Absolute neutrophil count (ANC) ≥ 1.500 /µl
• Leucocyte count ≥ lower normal limit
• Platelets ≥ 100.000 /µl and \<700.000 /µl
• Hemoglobin ≥ 6,0 mmol/l (regardless of prior transfusion)
• S-creatinine \< 140
• S-bilirubin ≤ 1,5 times upper normal limit

You may not qualify if:

• Patients will be excluded if they meet one of the criteria's listed below
• A history of prior malignancies. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 3 years after treatment.
• Known hypersensitivity to one of the active drugs or one or more of the excipients.
• Severe medical conditions, such as severe asthma/COLD, significant cardiac disease, poorly regulated insulin dependent diabetes mellitus among others.
• Creatinine clearance \< 70 ml/min (1).
• Acute/chronic infection with HIV, hepatitis, syphilis among others.
• Severe allergies or previous anaphylactic reactions.
• Active autoimmune disease, such as autoimmune neutropenia/thrombocytopenia or hemolytic anemia, systemic lupus erythematosis, Sjögren's syndrome, sclerodermia, myasthenia gravis, Goodpasteur's disease, Addison's disease, Hashimotos thyroiditis, active Graves disease.
• Subjects with history of myocarditis, regardless of etiology
• Troponin T (TnT) or I (TnI) \> 2x institutional upper limit of normal (ULN) is excluded. ii) between \> 1 to 2 x ULN will be permitted if a repeat assessment remains ≤ 2 x ULN and participant undergoes a cardiac evaluation and is cleared by a cardiologist or cardio-oncologist
• Prior treatment with LAG-3 targeted agents.
• Pregnant women and women breastfeeding.
• Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone, methotrexate among others) (2).
• Simultaneous treatment with other experimental drugs. Based on clinical judgement antihormonal treatment can be accepted.
• Simultaneous treatment with other systemic anti-cancer treatments.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (1)

National Center for Cancer Immune Therapy (CCIT-DK)

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Ipilimumab; Cyclophosphamide; fludarabine phosphate; Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: MD, PhD Tine Juul Monberg
• Organization: National Center for Cancer Immune Therapy (CCIT-DK)

tine.monberg@regionh.dk

38682983

Study Officials

• Inge Marie Svane, Prof., M.D.

  Study Director, National Center for Cancer Immune Therapy, Dept. of Oncology, Hospital Herlev

  STUDY DIRECTOR

• Tine J Monberg, M.D.

  Clinical Assistant, National Center for Cancer Immune Therapy, Dept. of Oncology, Hospital Herlev

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Professor

Model Details: 18 patients are included in 3 steps, containing 6 patients each. Step 1: 6 patients will be included. Ipilimumab wil not be administered 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 Step 2: 6 patients will be included. Ipilimumab will be administered once 2-6 weeks before tumor resection. Step 3: If no additional SAE/SAR, compared to the previous completed study at CCIT-DK, is observed additional 6 patients can be included at Step Two. If on the other hand Step 2 is not found safe, additional 6 patients can be included at Step 1

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 2, 2020
• Study Start: April 22, 2021
• Primary Completion: March 3, 2024
• Study Completion: March 3, 2024
• Last Updated: August 12, 2025
• Results First Posted: August 12, 2025

Record last verified: 2025-08

Locations

DK (1)