TNF-Inhibitor as Immune Checkpoint Inhibitor for Advanced MELanoma

NCT03293784 | Completed Phase 1 DMC

• 1 other identifier: 16CUTA07
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b, open-label study of immune checkpoints inhibitors Nivolumab+Ipilimumab administered in combination with the anti-TNF-α either Infliximab or Certolizumab, in patients with advanced melanoma.

Conditions

Melanoma

Keywords

Melanoma; Immune checkpoint; Nivolumab; Ipilimumab; Infliximab; Certolizumab; PD-1; TNFa; CTLA-4

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLT) incidence, in part 1 of the study.

  For each patient, DLT incidence will be evaluated during the Part 1 of the study: 12 weeks after the initial dose of study drug.

  12 weeks per patient (part 1)

Secondary Outcomes (3)

• Safety and tolerability according to the classification of the National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) Version 4.03.

  15 months per patient

• Progression Free Survival

  24 months per patient

• Objective Response Rate

  24 months per patient

Study Arms (2)

COHORT 1

OTHER

Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab

Combination Product: Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab

COHORT 2

OTHER

Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab

Combination Product: Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab

Interventions

Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab COMBINATION_PRODUCT

Induction phase: Nivolumab (1mg/kg) and Ipilimumab (3 mg/kg) injected at Week 0, 3, 6, and 9 with Certolizumab injected at the dose of 400mg at weeks 0, 3, and 6, and at the dose of 200mg at week 9. Maintenance phase: Nivolumab (3 mg/kg) alone injected from week 12 and then every 2 weeks with Certolizumab (200 mg) injected from week 12 and then every 2 weeks.

COHORT 1

Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab COMBINATION_PRODUCT

Induction phase: Nivolumab (1mg/kg) and Ipilimumab 3 mg/kg injected at Week 0, 3, 6, and 9 with Infliximab (5mg/kg) injected at weeks 0, 3 and 6. Maintenance phase: Nivolumab (3 mg/kg) alone injected from week 12 and then every 2 weeks with Infliximab (5mg/kg) injected from week 14 and then every 8 weeks.

COHORT 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with histologically-proven metastatic and/or unresectable melanoma (stage IIIc-IV, M1a-c as per AJCC 2009), including mucosal melanoma, without evidence of active intra-cranial disease.
• Subjects are included regardless of BRAFV600 mutation status. BRAFV600 mutation status must be documented.
• Measurable disease per RECIST 1.1
• Age ≥18 years and ≤70 years at the time of study entry.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Life expectancy of at least 3 months.
• Patient able to participate and willing to give informed consent prior to performance of any study-related procedures and to comply with the study protocol.
• Screening laboratory values must meet the following criteria and should be obtained prior to commencement of treatment:
• White blood count (WBC) ≥ 2000/μL Neutrophils ≥ 1500/μL Platelets ≥ 100 x103/μL Hemoglobin \> 9.0 g/dL
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85 / 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 / 72 x serum creatinine in mg/dL AST/ALT ≤ 3 x ULN (except subjects with hepatic metastasis, who can have AST/ALT ≤ 5 x ULN) Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Adequate cardiac and respiratory functions defined as New York Heart Association (NYHA) class 1 and SaO2 \> 90%.
• Patient must be naïve to systemic treatment for locally advanced and/or metastatic disease (i.e., no prior systemic anticancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant therapies (including Interferon α and Ipilimumab) is permitted if it was completed at least 12 weeks before start of treatment and all related AEs have either returned to baseline or stabilized.
• Prior radiotherapy or radiosurgery must have been completed at least 4 weeks prior to the first dose of the study treatment.
• Women of childbearing potential (WOCBP) must use two appropriate methods of contraception to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab/Ipilimumab to undergo five half-lives) after the last dose of investigational drug.

You may not qualify if:

• Patient pregnant, or breast-feeding.
• Uveal melanoma.
• Active and/or symptomatic intra cranial metastasis (including melanomatous meningitis). Patients with intra cranial metastasis may be eligible if all known lesions have been treated with stereotactic radiotherapy or surgery or both AND there has been no magnetic resonance imaging (MRI) evidence of disease progression in the CNS for ≥ 4 weeks after treatment and within 28 days prior the first dose of study drug administration.
• Previous treatment with B-RAF or MEK inhibitors within 12 weeks prior start of treatment.
• Hypersensitivity to the drugs of the study.
• Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Clinically significant cardiac dysfunction including congenital, familial, and genetic cardiac disorders, current instable angina, current symptomatic congestive heart failure of NYHA class 2 and higher, current uncontrolled hypertension ≥ grade 3; Left Ventricular Ejection Fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower.
• Patient with active malignancy other than melanoma or a history of previous within the past 3 years; except for patients with resected Basal cell carcinoma or resected Spindle cell carcinoma, resected carcinoma in situ of the cervix and resected carcinoma in situ of the breast.
• Active, known or suspected autoimmune disease including but not restricted to multiple sclerosis, optical nevritis and demyelinating neuropathy. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (HCV ribonucleic acid or HCV antibody) indicating acute or chronic infection.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Vaccination with any live attenuated conventional vaccine within the 3 months preceding the start of study treatment.
• Any current severe or uncontrolled disease, including, but not limited to ongoing or active infection.
• Patient included in another study with an experimental molecule and/or procedure.
• Unwillingness or inability to provide written informed consent.

Sponsors & Collaborators

• Institut Claudius Regaud: lead

Study Sites (1)

Institut Claudius Regaud IUCT-ONCOPOLE

Toulouse, 31059, France

Location

Related Publications (1)

• Montfort A, Filleron T, Virazels M, Dufau C, Milhes J, Pages C, Olivier P, Ayyoub M, Mounier M, Lusque A, Brayer S, Delord JP, Andrieu-Abadie N, Levade T, Colacios C, Segui B, Meyer N. Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase Ib Clinical Trial. Clin Cancer Res. 2021 Feb 15;27(4):1037-1047. doi: 10.1158/1078-0432.CCR-20-3449. Epub 2020 Dec 3.

  PMID: 33272982 RESULT

MeSH Terms

Conditions

Melanoma; Diabetes Mellitus, Insulin-Dependent, 12

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Nicolas MEYER

  Institut Claudius Regaud

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 26, 2017
• Study Start: October 16, 2017
• Primary Completion: December 6, 2019
• Study Completion: August 10, 2023
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

FR (1)