Neo-adjuvant Immunotherapy in Patients With Localized Melanoma

NCT07230613 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-IMM-25102025-522127-95-00
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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

Cutaneous Melanoma, Stage III; Mucosal Melanoma

Keywords

Neo-adjuvant Immunotherapy; Localized Cancers; Intra-tumoral treatment; Melanoma; Immune-checkpoint blockade

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Between 6 and 8 weeks upon end of the treatment

Study Arms (1)

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.

Drug: Ipilimumab (YervoyTM, 50 mg/10 mL solution); Drug: Nivolumab (OpdivoTM, 40 mg/4mL solution)

Interventions

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.

Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration

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.

Single Arm immunotherapy with Ipilimumab and nivolumab intra-tumoral administration

Eligibility Criteria

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

You may not qualify if:

• Patients ≥ 18 years old.
• Patients with resectable and measurable (according to RECIST v1.1 criteria) stage III cutaneous and mucosal melanoma.
• 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.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Gustave Roussy

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Solutions; Nivolumab

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

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Priyanka DEVI-MARULKAR, PhD, MBA

CONTACT

+33(0)662536043; p-devi-marulkar@unicancer.fr

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: November 17, 2025
• Study Start: January 12, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2033
• Last Updated: February 11, 2026

Record last verified: 2025-06

Locations

FR (1)