A MULTICENTER, SEEKING SIGNAL, RANDOMISED, OPEN-LABEL PHASE II OF RELATLIMAB AND NIVOLUMAB VS NIVOLUMAB ALONE IN LOCALLY ADVANCED CERVICAL CANCERS

NCT06715241 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: GINECO-CE111b2024-514032-25-00
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 30

Brief Summary

Multicenter, open-label, randomized, seeking signal (non-comparative), Phase II aiming to assess the clinical activity of the combination relatlimab + nivolumab in locally advanced cervical cancer eligible to standard CCRT

Conditions

LOCALLY ADVANCED CERVICAL CANCERS

Outcome Measures

Primary Outcomes (1)

• Primary outcome

  Objective response rate at the end of the 6-week induction period is defined as the rate of patients with CR or PR as per RECIST V1.1 at the end of the induction period. Response will be assessed according to RECIST v1.1 criteria as per investigator assessment. ORR-6w will be derived as a binary variable (success/failure), based on the following rules: * Patients showing an objective response based on RECIST tumoral evaluation performed at the end of the induction period will be considered in " success ". * Patients showing a progressive disease based on RECIST tumoral evaluation performed at the end of the induction period will be considered in " failure ". * Patients with no tumoral evaluation at the end of the induction period and with early death or clinical progression or treatment discontinuation due to toxicity will be considered in " failure ". * Patients who do not meet any of the conditions above will be consider as " non evaluable " for the primary endpoint.

  From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days

Secondary Outcomes (5)

• Progression Free survival (PFS)

  From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days

• Time to local progression (TTlP)

  From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days

• Time to metastatic progression (TTmP)

  From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days

• Overall Survival (OS)

  From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days

• ORR after CCRT/at the end of the maintenance period

  From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days

Study Arms (2)

Arm A: Nivolumab and relatlimab

EXPERIMENTAL

Combination Product: combination of relatlimab and nivolumab wich are two immunotherapy treatments

Arm B: Nivolumab only

OTHER

Other: Nivolumab alone

Interventions

Nivolumab alone OTHER

Induction: Nivolumab alone 360 mg, IV2 cycles (Q3W): 6 weeks Off treatment period: 4 to 6 weeks Maintenance: Nivolumab alone 480 mg, IV, 13 cycles (Q4W): 52 weeks

Arm B: Nivolumab only

combination of relatlimab and nivolumab wich are two immunotherapy treatments COMBINATION_PRODUCT

Induction: Nivolumab 360 mg/relatlimab 360 mg fixed dose combination, IV, 6 weeks Off treatment period: 4 to 6 weeks Maintenance: Nivolumab 480 mg/relatlimab 480 mg fixed dose combination, IV 13 cycles (Q4W): 52 weeks

Arm A: Nivolumab and relatlimab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged ≥18 years at time of inform consent signature.
• Patients must have histologically confirmed diagnosis of cervical squamous or adenosquamous carcinoma stage IIB to IVA according to FIGO 2018 (Appendix 1) and no evidence of metastatic disease (M0). Note: Nodal staging may be either surgical or by imaging (MRI/PET-CT) with pathological lymph node size defined by a short-axis diameter of ≥10mm (axial plane) or FDG uptake greater than that of the surrounding tissue and corresponding to the LN structure on CT when CT was performed for PETCT analysis.
• Patients must be naïve from prior anti-cancer treatment (all type) and eligible to standard CCRT as per standard practice and investigator' judgement.
• Known HPV status as per local assessment.
• Patient accepting to undergo a new cervix biopsy and with at least one lesion with a diameter ≥10 mm, visible by medical imaging and accessible to percutaneous sampling (needle biopsies 16 gauge or larger) that permit core needle biopsy (ideally 4 cores) without unacceptable risk of a major procedural complication.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 2).
• Adequate organ and marrow function with following lab values within 7 days before C1D1:
• Absolute neutrophil count (ANC) ≥1500/μL
• White blood cell (WBC) \>3000/μL
• Platelets ≥100 000/μL
• Hemoglobin (Hb) ≥9 g/dL
• Total bilirubin ≤1.5× upper limit of normal (ULN) unless due to Gilbert's syndrome
• ASAT /ALAT ≤3 ULN
• Creatinine ≤1.5 within normal limit, or
• Creatinine clearance ≥ 40 mL/min according to CKD-EPI formula (Appendix 3)

You may not qualify if:

• Evidence or treatment for another malignancy within 3 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed.
• History of severe allergic or other hypersensitivity reactions to:
• chimeric or humanized antibodies or fusion proteins,
• biopharmaceuticals produced in Chinese hamster ovary cells, or
• any component of the study treatments formulation.
• Patients with:
• Active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) unless their HBV is stably controlled on nucleoside analogs (eg entecavir or tenofovir) which will be continued for the duration of the study. Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to C1D1.
• Active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA, or
• HIV infection. Patients with prior organ or bone marrow transplant.
• Patients with active, suspected or history of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 5 for a more comprehensive list of pre-existing autoimmune diseases and immune deficiencies) with the following exceptions:
• patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone,
• patients with controlled Type 1 diabetes mellitus,
• patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• rash must cover less than 10% of body surface area (BSA).
• disease is well controlled at baseline and only requiring low potency topical steroids.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead

Study Sites (30)

ICO Paul Papin

Angers, 49055, France

Location

Sainte-Catherine Institut du Cancer Avignon-Provence

Avignon, 84918, France

Location

CHRU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

CHU de BREST - Hôpital Cavale Blanche

Brest, 29200, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Location

CHU de Dijon

Dijon, 21079, France

Location

Soumya.Anane@chicreteil.fr

Dijon, France

Location

CHRU Lille - Hôpital Jeanne de Flandre

Lille, 59000, France

Location

Centre Oscar Lambret

Lille, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Groupe Hospitalier Diaconesses - Croix Saint-Simon

Paris, 75012, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre CARIO - HPCA

Plérin, 22190, France

Location

CHU de Poitiers - Hôpital de la Milétrie

Poitiers, 86021, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

CHU Saint-Etienne - Pôle de Cancérologie

Saint-Etienne, 42271, France

Location

ICO - Centre René Gauducheau

Saint-Herblain, 44805, France

Location

ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, 67200, France

Location

CHU STRASBOURG - Hôpital de Hautepierre

Strasbourg, France

Location

Oncopole Claudius Regaud

Toulouse, 31059, France

Location

Recherche Oncologique Clinique 37 (ROC 37)

Tours, 37170, France

Location

ICL - Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 4, 2024
• Study Start: December 11, 2024
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

FR (30)