MelanomaPhase 1TICIMELNCT03293784
TNF-Inhibitor as Immune Checkpoint Inhibitor for Advanced MELanoma
A Phase 1 study testing Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab and Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab in people with Melanoma, run by Institut Claudius Regaud at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab and Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteFrance
- Study dates
- 16 Oct 2017to 10 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
- Men who are sexually active with WOCBP must use two contraceptive methods including at least one method with a failure rate of less than 1% per year for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.
- Absence of any psychological, familial, sociological or geographical condition that potentially hampers compliance with the study protocol and follow-up after treatment discontinuation schedule.
- Patient affiliated to a Social Health Insurance in France.
- Patient must provide written informed consent prior to any study specific procedures.
Who cannot join
- 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.
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- 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.
- History of untreated tuberculosis and/or positive quantiferon test without previous prophylaxis tuberculosis treatment, or untreated active infection with mycobacterium tuberculosis. For patients with asymptomatic (including radiologic symptoms) infection with mycobacterium tuberculosis, inclusion may be possible after 4 weeks of adequate antibiotics treatment.
- 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.
- Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the compliance of treatment and the study protocol.
- Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: TNF-Inhibitor as Immune Checkpoint Inhibitor for Advanced MELanoma - A Phase Ib Clinical Study
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.
Read the detailed description
The study will be conducted in 2 consecutive parts:
- Part 1 with 2 parallel cohorts (Nivolumab+Ipilimumab administered in combination with anti-TNF-α Certolizumab (Cohort 1) and Nivolumab+Ipilimumab administered in combination with anti-TNF-α Infliximab (Cohort 2)). 6 patients will be included in each cohort.
- Part 2 (expansion phase) will then be scheduled after the most promising combination has been confirmed; the choice of the combination will be based on safety, efficacy, and PD data observed in both cohorts during the Part 1 of the study.
- Conditions
- Melanoma
- Being tested
- Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab, Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab
- Keywords
- Melanoma, Immune checkpoint, Nivolumab, Ipilimumab, Infliximab, Certolizumab, PD-1, TNFa, CTLA-4
- Medical subject headings
- Melanoma, Diabetes Mellitus, Insulin-Dependent, 12
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab+Ipilimumab in combination with Anti TNF-α CertolizumabCombination 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.
Nivolumab+Ipilimumab in combination with Anti TNF-α InfliximabCombination 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.
| Study group | Role | What they receive |
|---|---|---|
| COHORT 1 | Other | Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab Receives: Combination Product: Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab |
| COHORT 2 | Other | Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab Receives: Combination Product: Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
The assessment of safety and tolerability will be based on the incidence of Adverse Events (AEs), Serious Adverse Events, AEs leading to discontinuation, and death. In addition, clinical laboratory test abnormalities will be examined. Tolerability will be evaluated by collecting dose interruptions and dose delays.
Measured: 15 months per patient
Progression Free Survival
Progression Free Survival (PFS) is defined as the time from inclusion until progression or deaths; patients alive at last follow-up news are censored at this date.
Measured: 24 months per patient
Objective Response Rate
Objective Response Rate (ORR) is defined as the number of patients with Best Overall Response divided by the number of included patients in each cohort.
Measured: 24 months per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start16 Oct 2017
- Primary completion6 Dec 2019
- Study completion10 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Claudius Regaud
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas MEYER, Principal investigator, Institut Claudius Regaud
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03293784
- Sponsor's protocol ID
- 16CUTA07
- Acronym
- TICIMEL
- Status last verified
- Mar 2026
- First submitted
- 20 Sep 2017
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33272982Dufau C, Genais M, Mucher E, Jung B, Garcia V, Montfort A, Tosolini M, Clarke CJ, Medin JA, Levade T, Delord JP, Meyer N, Pancaldi V, Andrieu-Abadie N, Segui B. Ceramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients. Front Immunol. 2024 Jul 29;15:1421432. doi: 10.3389/fimmu.2024.1421432. eCollection 2024.
PubMed 39136013
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TNF-Inhibitor as Immune Checkpoint Inhibitor for Advanced MELanoma - A Phase Ib Clinical Study
- ClinicalTrials.gov ID
- NCT03293784
- Acronym / sponsor ID
- TICIMEL / 16CUTA07
- Conditions
- Melanoma
- Keywords
- Melanoma, Immune checkpoint, Nivolumab, Ipilimumab, Infliximab, Certolizumab, PD-1, TNFa
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Institut Claudius RegaudUniversity, hospital or other
- Study start
- 16 Oct 2017 (actual)
- Primary completion
- 6 Dec 2019 (actual)
- Study completion
- 10 Aug 2023 (actual)
- First posted
- 26 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study will be conducted in 2 consecutive parts:
- Part 1 with 2 parallel cohorts (Nivolumab+Ipilimumab administered in combination with anti-TNF-α Certolizumab (Cohort 1) and Nivolumab+Ipilimumab administered in combination with anti-TNF-α Infliximab (Cohort 2)). 6 patients will be included in each cohort.
- Part 2 (expansion phase) will then be scheduled after the most promising combination has been confirmed; the choice of the combination will be based on safety, efficacy, and PD data observed in both cohorts during the Part 1 of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| COHORT 1 | Other | Combination Product: Nivolumab+Ipilimumab in combination with Anti TNF-α CertolizumabNivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab |
| COHORT 2 | Other | Combination Product: Nivolumab+Ipilimumab in combination with Anti TNF-α InfliximabNivolumab+Ipilimumab in combination with Anti TNF-α Infliximab |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab+Ipilimumab in combination with Anti TNF-α CertolizumabInduction 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. | Combination product | COHORT 1 |
| Nivolumab+Ipilimumab in combination with Anti TNF-α InfliximabInduction 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. | Combination product | COHORT 2 |
Primary outcome
Dose Limiting Toxicities (DLT) incidence, in part 1 of the study.
Time frame: 12 weeks per patient (part 1)
For each patient, DLT incidence will be evaluated during the Part 1 of the study: 12 weeks after the initial dose of study drug.
3 secondary outcomes
Safety and tolerability according to the classification of the National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) Version 4.03.
Time frame: 15 months per patient
Progression Free Survival
Time frame: 24 months per patient
Objective Response Rate
Time frame: 24 months per patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Results publication: PubMed 33272982Montfort 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.
- Derived from this study: PubMed 39136013Dufau C, Genais M, Mucher E, Jung B, Garcia V, Montfort A, Tosolini M, Clarke CJ, Medin JA, Levade T, Delord JP, Meyer N, Pancaldi V, Andrieu-Abadie N, Segui B. Ceramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients. Front Immunol. 2024 Jul 29;15:1421432. doi: 10.3389/fimmu.2024.1421432. eCollection 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas MEYER principal investigator
Institut Claudius Regaud
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab+Ipilimumab in combination with Anti TNF-α Certolizumab and Nivolumab+Ipilimumab in combination with Anti TNF-α Infliximab in people with Melanoma, run by Institut Claudius Regaud at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicities (DLT) incidence, in part 1 of the study. (time frame: 12 weeks per patient (part 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03293784, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.