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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jun 2025 → ongoing

Decision date (initial)

2025-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To study event-free survival (EFS) in patients with resectable stage III melanoma, receiving two different neoadjuvant immune checkpoint inhibitor (ICI) regimens, combined anti-CTLA-4/anti-PD-1 blockade or anti-PD-1 monotherapy.

Secondary objectives 1

1. Further efficacy and safety analysis, including RFS, DMFS, OS and MPR

Conditions and MedDRA coding

Malignant melanoma stage III

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 a. 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. b. Patients with cutaneous, acral, or unknown primary melanomas are eligible for enrollment. c. 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: a. 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; b. hormonal (oral, intravaginal, transdermal, implantable or injectable) c. an intrauterine hormone-releasing system (IUS) d. 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 6

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 (including operation), 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 9

1. 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.
2. 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.
3. Overall survival (OS), defined as time between date of randomization and date of death.
4. 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.
5. Correlation of pathologic response in each arm to RFS, DMFS, and OS.
6. Correlation of radiological and clinical response evaluation to RFS, DMFS, and OS.
7. Proportion of patients having surgery according to plan (within 10 weeks from first neoadjuvant course).
8. Surgical complication rates according to Clavien-Dindo surgical classification.
9. Frequency and duration of all grade and grade 3-5 treatment-related adverse events (AEs) according to CTCAE 5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Hildur Helgadpttir

Public contact point

Organisation

Karolinska University Hospital

Contact name

Hildur Helgadpttir

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications