SWE-NEO: Swedish NeoAdjuvant Trial Comparing Monotherapy to Combined Immunotherapy in Resectable Stage III Melanoma (SWE-NEO)

December 11, 2025 updated by: Hildur Helgadottir

SWE-NEO: Swedish NeoAdjuvant Trial Comparing Anti-PD-1 Monotherapy to Combined Anti-CTLA-4/Anti-PD-1 Blockade in Resectable Stage III Melanoma

At present two studies (SWOG S1801 and NADINA) have demonstrated superiority when using neoadjuvant treatment compared to adjuvant treatment only, but no studies have compared PD-1 monotherapy (SWOG 1801 regimen) to the PD-1/CTLA-4 combination (NADINA regimen) therapy. The SWE-NEO study aims to compare these two regimens, where the PD-1/CTLA-4 combination is potentially more effective, but also associated with more side effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A phase III randomized controlled multicenter open-label trial. Patients will be randomized after a diagnosis of resectable stage III melanoma to have either two courses of CTLA-4 and PD-1 inhibitor combination therapy or PD-1 inhibitor monotherapy, before the pre-planned operation. In both arms, adjuvant treatment with a PD-1 inhibitor or with BRAF+MEK inhibitors in patients with a BRAF V600E mutation, will be given only to patients with no major pathological response in the operated tumor, with PD-1 inhibitor, or with BRAF+MEK inhibitors in patients with BRAF V600E mutation. Active follow-up will be performed for 3 years from surgery and followed for survival up until 10 years. Sequential blood and tumor samples will be collected for biomarker analyses.

Study Type

Interventional

Enrollment (Estimated)

128

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Sweden
      • Gothenburg, Sweden
        • Recruiting
        • Sahlgrenska University Hospital
        • Contact:
      • Lund, Sweden
      • Stockholm, Sweden
        • Recruiting
        • Karolinska University Hospital
        • Principal Investigator:
          • Hildur Helgadottir, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participants must be at least 18 years of age.
  2. Can provide a signed informed consent as described in the protocol, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
  3. World Health Organization (WHO) Performance Status 0 or 1.

  4. Patients must have

    1. Histologically or cytologically confirmed Stage III melanoma. In the case of in-transit metastases (with or without lymph node metastases)' ≤3 resectable in-transit metastases are allowed.
    2. Patients with cutaneous, acral, or unknown primary melanomas are eligible for enrollment.
    3. Resectable tumors are defined as having no significant vascular, neural or bony involvement. Only patients where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable.
  5. Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

  6. Female patients of childbearing potential must be willing to use a highly effective method of contraception, for the course of the study through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Highly effective methods of contraception include one or more of the following:

    1. male partner who is sterile (vasectomised) prior to the female study subject's entry into the study and is the sole sexual partner for the female subject;
    2. hormonal (oral, intravaginal, transdermal, implantable or injectable)
    3. an intrauterine hormone-releasing system (IUS)
    4. an intrauterine device (IUD) with a documented failure rate of < 1%.
  7. Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. A unique female sexual partner must postmenopausal, permanently sterilized (e.g. hysterectomy or tubal ligation), or use a highly effective method of contraception.
  8. No other malignancies, except if treated with curative intent and with a cancer-related life expectancy of more than 5 years.
  9. No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1.
  10. No prior targeted therapy targeting BRAF and/or MEK.

Exclusion Criteria:

  1. Unresectable melanoma
  2. Uveal/ocular or mucosal melanoma
  3. Any serious or uncontrolled medical conditions that, in the investigator's opinion, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results .
  4. Subjects with a 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.
  5. Women who are pregnant or breastfeeding.
  6. Any condition that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before registration in the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PD-1 inhibitor monotherapy
Monotherapy with Nivolumab
Drug: Nivolumab
Adjuvant monotherapy with Nivolumab
Experimental: PD-1/CTLA-4 inhibitor combination therapy
Combination therapy with Nivolumab and Ipilimumab
Drug: Nivolumab + Ipilimumab
Adjuvant combination therapy with Nivolumab and Ipilimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Event-free survival (EFS), defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, or death from any cause (treatment-related, melanoma related or any other).
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-free survival (RFS)
Time Frame: From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Relapse-free survival (RFS), defined as time between date of surgery and date of melanoma recurrence, treatment-related death or melanoma-related death, whichever occurs first.
From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Distant metastasis-free survival (DMFS)
Time Frame: From date of randomization until the date of first documented distant metastasis or date of death from any cause, whichever came first, assessed up to 60 months
Distant metastasis-free survival (DMFS), defined as time between date of randomization and date of first distant metastasis, treatment-related death or melanoma-related death, whichever occurs first.
From date of randomization until the date of first documented distant metastasis or date of death from any cause, whichever came first, assessed up to 60 months
Overall survival (OS)
Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months
Overall survival (OS), defined as time between date of randomization and date of death.
From date of randomization until the date of death from any cause, assessed up to 60 months
Major pathological response (MPR)
Time Frame: Start of neoadjuvant therapy to end of neoadjuvant therapy, up to approximately two months
Major pathological response (MPR) (≤10% viable tumor cells), difference in MPR between combined ICI and monotherapy, central review of all surgical specimens by three expert melanoma pathologists.
Start of neoadjuvant therapy to end of neoadjuvant therapy, up to approximately two months
Correlation of pathologic response to RFS, DMFS, and OS
Time Frame: From end of neoadjuvant therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Correlation of pathologic response in each arm to RFS, DMFS, and OS.
From end of neoadjuvant therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Correlation of response to RFS, DMFS, and OS
Time Frame: From end of neoadjuvant therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Correlation of radiological and clinical response evaluation to RFS, DMFS, and OS.
From end of neoadjuvant therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Proportion of patients having surgery according to plan
Time Frame: From start of neoadjuvant therapy to date of surgery, assessed up to 6 months
Number of patients having surgery according to plan (within 10 weeks from first neoadjuvant course).
From start of neoadjuvant therapy to date of surgery, assessed up to 6 months
Surgical complication rates
Time Frame: From surgery to date of any postoperative complication, assessed up to 3 months post surgery
Surgical complication rates according to Clavien-Dindo surgical classification.
From surgery to date of any postoperative complication, assessed up to 3 months post surgery
Frequency of treatment-related adverse events (AEs)
Time Frame: From start of neoadjuvant therapy up to 1 year after last treatment
Frequency of all grade and grade 3-5 treatment-related adverse events (AEs) according to CTCAE 5.0.
From start of neoadjuvant therapy up to 1 year after last treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of different biological markers with treatment efficacy and safety
Time Frame: From start of neoadjuvant therapy to last blood/tumour sample taken, until the date of first documented progression, assessed up to 60 months

The explorative endpoints of this trial are:

Correlation of different biological markers analyzed from sequential blood and tumor samples with treatment efficacy and safety.
From start of neoadjuvant therapy to last blood/tumour sample taken, until the date of first documented progression, assessed up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hildur Helgadottir

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2025

Primary Completion (Estimated)

April 15, 2032

Study Completion (Estimated)

April 15, 2032

Study Registration Dates

First Submitted

January 16, 2025

First Submitted That Met QC Criteria

January 22, 2025

First Posted (Actual)

January 27, 2025

Study Record Updates

Last Update Posted (Actual)

December 12, 2025

Last Update Submitted That Met QC Criteria

December 11, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SWE-NEO Trial

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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