Clinical trial · Interventional
Neo-adjuvant Immunotherapy in Patients With Localized Melanoma
Neo-adjuvant Intratumoral Anti-CTLA4 + Anti-PD1 in Patients With Localized Melanoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Cutaneous Melanoma, Stage III | Cutaneous Melanoma | CURATED_BROADER | 0.78 |
| Mucosal Melanoma | Mucosal Melanoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Ipilimumab (YervoyTM, 50 mg/10 mL solution) | Drug | Ipilimumab | ALIAS |
| Nivolumab (OpdivoTM, 40 mg/4mL solution) | Drug | Nivolumab | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration
- description
- 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.
- interventionNames
- Drug: Ipilimumab (YervoyTM, 50 mg/10 mL solution)
- Drug: Nivolumab (OpdivoTM, 40 mg/4mL solution)
Primary outcomes (2)
- 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.
- timeFrame
- Between 6 and 8 weeks upon end of the treatment
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
In addition to NEOREM Master Protocol inclusion and exclusion criteria, the following inclusion and exclusion criteria must be verified before inclusion in the NEO-1 trial: Inclusion Criteria: 1. Patients ≥ 18 years old. 2. Patients with resectable and measurable (according to RECIST v1.1 criteria) stage III cutaneous and mucosal melanoma. 3. Patients who received anti-PD-1 and stopped treatment \> 6 months prior to their inclusion in NEO-1 trial are eligible. 4. Patients who received target therapy and stopped treatment \> 3 months prior to their inclusion in NEO-1 trial are eligible. Exclusion Criteria: 1. Patients with clinically or radiologically detectable distant metastases. 2. Patients with uveal melanoma. 3. Patients with any hypersensitivity to the active ingredient or to any of the excipients of nivolumab and/ ipilimumab. 4. Patients without pathological evaluable disease according to RECIST v1.1 criteria.
References
Publications (0)
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