Cutaneous Melanoma, Stage IIIPhase 2NEOREM-NEO-1NCT07230613
Neo-adjuvant Immunotherapy in Patients With Localized Melanoma
A Phase 2 study testing Ipilimumab (YervoyTM, 50 mg/10 mL solution) and Nivolumab (OpdivoTM, 40 mg/4mL solution) in people with Cutaneous Melanoma, Stage III and Mucosal Melanoma, run by UNICANCER at 6 sites in France.
Trial summary
The success of anti-PD-1 and anti-CTLA-4 therapies has initiated a paradigm shift in oncology, with drugs now targeting the immune system rather than cancer cells to stimulate the antitumor immune response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Melanoma, Stage III, Mucosal Melanoma
- What is being tested?
- Ipilimumab (YervoyTM, 50 mg/10 mL solution) and Nivolumab (OpdivoTM, 40 mg/4mL solution)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 6 sitesFrance
- Study dates
- 12 Jan 2026to Dec 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years old.
- Patients with resectable and measurable (according to RECIST v1.1 criteria) stage III cutaneous and mucosal melanoma.
- Patients who received anti-PD-1 and stopped treatment > 6 months prior to their inclusion in NEO-1 trial are eligible.
- Patients who received target therapy and stopped treatment > 3 months prior to their inclusion in NEO-1 trial are eligible.
Who cannot join
- Patients with clinically or radiologically detectable distant metastases.
- Patients with uveal melanoma.
- Patients with any hypersensitivity to the active ingredient or to any of the excipients of nivolumab and/ ipilimumab.
- Patients without pathological evaluable disease according to RECIST v1.1 criteria.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
France6 sites, 6 recruiting
- Recruiting
CHU de Bordeaux- Hôpital Saint-André
Bordeaux, 33075
Caroline DUTRIAUX, MD, PhD, +33 05 56 79 47 05, caroline.dutriaux@chu-bordeaux.fr
Caroline DUTRIAUX, MD, PHD
- Recruiting
Centre Léon Bérard
Lyon, 69373
Mona AMINI-ADLE, MD, PhD, +33 04 78 78 59 96, Mona.AMINI-ADLE@lyon.unicancer.fr
Mona AMINI-ADLE, MD, PHD
- Recruiting
Hospices Civils de Lyon (Hôpital Lyon Sud)
Lyon, 69495
Stéphane DALLE, MD, PhD, +33 04 78 86 16 79, stephane.dalle@chu-lyon.fr
Stéphane DALLE, MD, PHD
- Recruiting
AP-HM Marseille (Hôpital de la Timone)
Marseille, 13005
Caroline GAUDY-MARQUESTE, MD, PhD, +33 04 91 38 57 80, caroline.gaudy@ap-hm.fr
Caroline GAUDY-MARQUESTE, MD, PHD
- Recruiting
AP-HP- Hôpital Saint-Louis
Paris, 75010
Céleste LEBBÉ, MD, PhD, +33 01 42 49 93 92, celeste.lebbe@aphp.fr
Céleste LEBBÉ, MD, PHD
- Recruiting
Gustave Roussy
Villejuif, 94805
Caroline ROBERT, MD, PhD, 33(0) 1 42 11 42 53, Caroline.ROBERT@gustaveroussy.fr
Caroline ROBERT, MD, PHD
About this study
Official title: Neo-adjuvant Intratumoral Anti-CTLA4 + Anti-PD1 in Patients With Localized Melanoma
The success of anti-PD-1 and anti-CTLA-4 therapies has initiated a paradigm shift in oncology, with drugs now targeting the immune system rather than cancer cells to stimulate the antitumor immune response. Intratumoral (IT) delivery of immunostimulating agents reduces the systemic toxicity associated with monoclonal antibodies (mAbs) targeting immune checkpoints. Notably, IT injections of immune checkpoint blockade (ICB) have been shown to induce immune-mediated tumor responses both at the injected site and at distant, non-injected tumor sites. While surgery has traditionally been the preferred treatment for stage III and IV melanoma patients, neoadjuvant therapy with anti-CTLA-4 and anti-PD-1 agents has shown promising efficacy.
In patients with localized melanoma, it is hypothesized that IT administration of ipilimumab (anti-CTLA-4 Ab) combined with nivolumab (anti-PD-1 Ab) will provide the most effective and safe treatment combination.
Read more
The NEO-1 study is a proof-of-concept clinical trial designed as a sub-protocol of NEOREM master protocol (NCT07262489) to validate the intratumoral immunotherapy approach, aiming to maximize the dose/efficacy ratio of combined ipilimumab and nivolumab treatment while minimizing systemic adverse events. This is an academic, open-label, multicentric, phase II clinical trial evaluating the efficacy and safety of intratumoral injections of ipilimumab and nivolumab combination as neoadjuvant treatment in localized stage III resectable cutaneous or mucosal melanoma patients.
Baseline and on-treatment PORTRAIT profiling, as described in the NEOREM Master Protocol (NCT07262489), will be performed using fresh blood and tumor samples. This profiling will reveal the immune status of patients and support biomarker-driven preselection for future trials.
Read the detailed description
The combination of ipilimumab + nivolumab injected intravenously before resection of resectable stage III melanoma is more effective than adjuvant immunotherapy as recently demonstrated in a large phase III randomized controlled trial. However, the dual systemic immunotherapy gives rise to severe AEs (30% of patients had > grade 3 related AEs versus 14% in the adjuvant arm). NEO-1, a prospective, multicenter, phase II sub-protocol of the NEOREM master protocol (NCT07262489) focuses on evaluating the efficacy and safety of intratumoral neo-adjuvant treatment with ipilimumab and nivolumab in patients with resectable stage III melanoma.
NEO-1 is a proof-of-concept study designed to validate human intratumoral immunotherapy (HIT-IT) approach, which could maximize its dose/efficacy ratio of combined ipilimumab and nivolumab treatment while preventing systemic AEs. Image guided drug administration directly into tumor will increase the drug concentration at the tumor site leading to targeted drug action.
While evaluating the efficacy of intratumoral administration of ipilimumab in combination with nivolumab in melanoma patients, the NEO-1 study employs PORTRAIT profiling to analyze fresh blood and tumor samples collected at baseline and throughout treatment. This approach will reveal the features of the tumor microenvironment both before and after surgery, facilitating the identification of biomarkers that predict the efficacy of the proposed immunotherapy. The NEOREM master protocol (NCT07262489) allows the rapid analyses of the fresh samples collected, which enables an actual characterization of the immune landscape in patients prior to and during treatment.
- Conditions
- Cutaneous Melanoma, Stage III, Mucosal Melanoma
- Being tested
- Ipilimumab (YervoyTM, 50 mg/10 mL solution), Nivolumab (OpdivoTM, 40 mg/4mL solution)
- Keywords
- Neo-adjuvant Immunotherapy, Localized Cancers, Intra-tumoral treatment, Melanoma, Immune-checkpoint blockade
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ipilimumab (YervoyTM, 50 mg/10 mL solution)Drug
The 25 mg flat dose of the Ipilimumab will be administered by intra-tumoral injection. Injections will be performed under image guidance (the most adequate according to investigators preference). Ultrasound guidance will be privileged, as it is not using radiation. A maximum of 3 intratumoral procedures may occur with 3 weeks intervals prior to surgery.
Nivolumab (OpdivoTM, 40 mg/4mL solution)Drug
The 30 mg flat dose of the Nivolumab will be administered by intra-tumoral injection. Injections will be performed under image guidance (the most adequate according to investigators preference). Ultrasound guidance will be privileged, as it is not using radiation. A maximum of 3 intratumoral procedures may occur with 3 weeks intervals prior to surgery.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration | Experimental | Patients will receive up to 3 doses of neo-adjuvant treatment with IT injections of ipilimumab (5mg/mL) \& nivolumab (10mg/mL) at 3-week intervals (±3 days) for up to 6 weeks prior to surgery. Receives: Drug: Ipilimumab (YervoyTM, 50 mg/10 mL solution); Drug: Nivolumab (OpdivoTM, 40 mg/4mL solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to evaluate the efficacy of the intratumoral combination of ipilimumab and nivolumab in terms of pCR or MPR in patients with resectable stage III cutaneous or mucosal melanoma.
The primary efficacy endpoint is defined as a pathological complete response (pCR) rate defined as the percentage of patients with pCR defined as the complete absence of viable tumor cells, or the major pathologic response (MPR) defined as less than 10% of surviving tumor cells in tumor biopsy of the surgical specimen.
Measured: Between 6 and 8 weeks upon end of the treatment
The primary objective is to evaluate the tolerability of the intratumoral combination of ipilimumab and nivolumab in patients with resectable stage III cutaneous or mucosal melanoma.
The primary safety endpoint defined as the percentage of patients whose surgery was delayed by more than 2 weeks beyond the planned timeline, due to treatment-related adverse events.
Measured: Between 6 and 8 weeks upon end of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2025
- Study start12 Jan 2026
- Primary completionDec 2027 (estimated)
- Study completionDec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Melanoma, Stage IIIStudies of the same condition, open and under way.
- More trials run by UNICANCERThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- NEO-1 is an academic, non-comparative, non-randomized, multicenter Phase II clinical trial evaluating the effectiveness and safety of intratumoral injections of ipilimumab combined with nivolumab as a neoadjuvant treatment for patients with operable, localized stage III cutaneous or mucosal melanoma. Eligible patients in the NEOREM master protocol and its therapeutic sub-protocol i.e. NEO-1 trial will receive three injections of the ipilimumab and nivolumab combination, one injection every three weeks over six weeks prior to surgery. Surgery will take place between 6 and 8 weeks after the last intratumoral injection. If deemed necessary by the doctor, some patients may receive standard adjuvant treatment after surgery. Patient participation in the trial will not exceed 65 months from their selection into NEOREM and inclusion in NEO-1 including the treatment, surgery and post-surgery follow-up.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07230613
- Sponsor's protocol ID
- UC-IMM-2510
- Other IDs
- 2025-522127-95-00, 2025
- Acronym
- NEOREM-NEO-1
- Status last verified
- Jul 2026
- First submitted
- 26 Sep 2025
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neo-adjuvant Intratumoral Anti-CTLA4 + Anti-PD1 in Patients With Localized Melanoma
- ClinicalTrials.gov ID
- NCT07230613
- Acronym / sponsor ID
- NEOREM-NEO-1 / UC-IMM-2510
- Conditions
- Cutaneous Melanoma, Stage III, Mucosal Melanoma
- Keywords
- Neo-adjuvant Immunotherapy, Localized Cancers, Intra-tumoral treatment, Melanoma, Immune-checkpoint blockade
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Study start
- 12 Jan 2026 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2033 (estimated)
- First posted
- 17 Nov 2025 (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.
The success of anti-PD-1 and anti-CTLA-4 therapies has initiated a paradigm shift in oncology, with drugs now targeting the immune system rather than cancer cells to stimulate the antitumor immune response. Intratumoral (IT) delivery of immunostimulating agents reduces the systemic toxicity associated with monoclonal antibodies (mAbs) targeting immune checkpoints. Notably, IT injections of immune checkpoint blockade (ICB) have been shown to induce immune-mediated tumor responses both at the injected site and at distant, non-injected tumor sites. While surgery has traditionally been the preferred treatment for stage III and IV melanoma patients, neoadjuvant therapy with anti-CTLA-4 and anti-PD-1 agents has shown promising efficacy.
In patients with localized melanoma, it is hypothesized that IT administration of ipilimumab (anti-CTLA-4 Ab) combined with nivolumab (anti-PD-1 Ab) will provide the most effective and safe treatment combination.
The NEO-1 study is a proof-of-concept clinical trial designed as a sub-protocol of NEOREM master protocol (NCT07262489) to validate the intratumoral immunotherapy approach, aiming to maximize the dose/efficacy ratio of combined ipilimumab and nivolumab treatment while minimizing systemic adverse events. This is an academic, open-label, multicentric, phase II clinical trial evaluating the efficacy and safety of intratumoral injections of ipilimumab and nivolumab combination as neoadjuvant treatment in localized stage III resectable cutaneous or mucosal melanoma patients.
Baseline and on-treatment PORTRAIT profiling, as described in the NEOREM Master Protocol (NCT07262489), will be performed using fresh blood and tumor samples. This profiling will reveal the immune status of patients and support biomarker-driven preselection for future trials.
Detailed description
The combination of ipilimumab + nivolumab injected intravenously before resection of resectable stage III melanoma is more effective than adjuvant immunotherapy as recently demonstrated in a large phase III randomized controlled trial. However, the dual systemic immunotherapy gives rise to severe AEs (30% of patients had > grade 3 related AEs versus 14% in the adjuvant arm). NEO-1, a prospective, multicenter, phase II sub-protocol of the NEOREM master protocol (NCT07262489) focuses on evaluating the efficacy and safety of intratumoral neo-adjuvant treatment with ipilimumab and nivolumab in patients with resectable stage III melanoma.
NEO-1 is a proof-of-concept study designed to validate human intratumoral immunotherapy (HIT-IT) approach, which could maximize its dose/efficacy ratio of combined ipilimumab and nivolumab treatment while preventing systemic AEs. Image guided drug administration directly into tumor will increase the drug concentration at the tumor site leading to targeted drug action.
While evaluating the efficacy of intratumoral administration of ipilimumab in combination with nivolumab in melanoma patients, the NEO-1 study employs PORTRAIT profiling to analyze fresh blood and tumor samples collected at baseline and throughout treatment. This approach will reveal the features of the tumor microenvironment both before and after surgery, facilitating the identification of biomarkers that predict the efficacy of the proposed immunotherapy. The NEOREM master protocol (NCT07262489) allows the rapid analyses of the fresh samples collected, which enables an actual characterization of the immune landscape in patients prior to and during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- NEO-1 is an academic, non-comparative, non-randomized, multicenter Phase II clinical trial evaluating the effectiveness and safety of intratumoral injections of ipilimumab combined with nivolumab as a neoadjuvant treatment for patients with operable, localized stage III cutaneous or mucosal melanoma. Eligible patients in the NEOREM master protocol and its therapeutic sub-protocol i.e. NEO-1 trial will receive three injections of the ipilimumab and nivolumab combination, one injection every three weeks over six weeks prior to surgery. Surgery will take place between 6 and 8 weeks after the last intratumoral injection. If deemed necessary by the doctor, some patients may receive standard adjuvant treatment after surgery. Patient participation in the trial will not exceed 65 months from their selection into NEOREM and inclusion in NEO-1 including the treatment, surgery and post-surgery follow-up.
| Arm | Type | Receives |
|---|---|---|
| Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration | Experimental | Drug: Ipilimumab (YervoyTM, 50 mg/10 mL solution), Drug: Nivolumab (OpdivoTM, 40 mg/4mL solution)Patients will receive up to 3 doses of neo-adjuvant treatment with IT injections of ipilimumab (5mg/mL) \& nivolumab (10mg/mL) at 3-week intervals (±3 days) for up to 6 weeks prior to surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients ≥ 18 years old.
- Patients with resectable and measurable (according to RECIST v1.1 criteria) stage III cutaneous and mucosal melanoma.
- Patients who received anti-PD-1 and stopped treatment > 6 months prior to their inclusion in NEO-1 trial are eligible.
- Patients who received target therapy and stopped treatment > 3 months prior to their inclusion in NEO-1 trial are eligible.
Key exclusion criteria (4 listed)
- Patients with clinically or radiologically detectable distant metastases.
- Patients with uveal melanoma.
- Patients with any hypersensitivity to the active ingredient or to any of the excipients of nivolumab and/ ipilimumab.
- Patients without pathological evaluable disease according to RECIST v1.1 criteria.
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 |
|---|---|---|
| Ipilimumab (YervoyTM, 50 mg/10 mL solution)The 25 mg flat dose of the Ipilimumab will be administered by intra-tumoral injection. Injections will be performed under image guidance (the most adequate according to investigators preference). Ultrasound guidance will be privileged, as it is not using radiation. A maximum of 3 intratumoral procedures may occur with 3 weeks intervals prior to surgery. | Drug | Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration |
| Nivolumab (OpdivoTM, 40 mg/4mL solution)The 30 mg flat dose of the Nivolumab will be administered by intra-tumoral injection. Injections will be performed under image guidance (the most adequate according to investigators preference). Ultrasound guidance will be privileged, as it is not using radiation. A maximum of 3 intratumoral procedures may occur with 3 weeks intervals prior to surgery. | Drug | Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration |
Primary outcome
The primary objective is to evaluate the efficacy of the intratumoral combination of ipilimumab and nivolumab in terms of pCR or MPR in patients with resectable stage III cutaneous or mucosal melanoma.
Time frame: Between 6 and 8 weeks upon end of the treatment
The primary efficacy endpoint is defined as a pathological complete response (pCR) rate defined as the percentage of patients with pCR defined as the complete absence of viable tumor cells, or the major pathologic response (MPR) defined as less than 10% of surviving tumor cells in tumor biopsy of the surgical specimen.
The primary objective is to evaluate the tolerability of the intratumoral combination of ipilimumab and nivolumab in patients with resectable stage III cutaneous or mucosal melanoma.
Time frame: Between 6 and 8 weeks upon end of the treatment
The primary safety endpoint defined as the percentage of patients whose surgery was delayed by more than 2 weeks beyond the planned timeline, due to treatment-related adverse events.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
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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.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab (YervoyTM, 50 mg/10 mL solution) and Nivolumab (OpdivoTM, 40 mg/4mL solution) in people with Cutaneous Melanoma, Stage III and Mucosal Melanoma, run by UNICANCER at 6 sites 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 4 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Priyanka DEVI-MARULKAR, PhD, MBA (+33(0)662536043, p-devi-marulkar@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to evaluate the efficacy of the intratumoral combination of ipilimumab and nivolumab in terms of pCR or MPR in patients with resectable stage III cutaneous or mucosal melanoma. (time frame: Between 6 and 8 weeks upon end of the treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Jul 2026.