One-dose pembrolizumab before surgery for thick primary (Stage IIb/c) melanoma

Neoadjuvant Pembrolizumab in Patients With Stage IIb/c Melanoma, a Phase II Double-blind Placebo-controlled Randomized Trial

This trial tests whether giving one dose of pembrolizumab before surgery helps adults with biopsy-proven Stage IIb/c primary cutaneous melanoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vastra Gotaland Region (Government)
• Drugs / interventions: immunotherapy, prednisone, pembrolizumab
• Locations: 1 site (Gothenburg)
• Trial ID: NCT07349303 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase II trial for patients with biopsy-confirmed thick primary melanoma without clinical lymph-node involvement. Eligible patients undergo a 3 mm punch biopsy to confirm diagnosis and are randomized to a single 400 mg dose of pembrolizumab or placebo. Four weeks after the dose they have wide local excision and sentinel lymph node biopsy according to national guidelines. The primary endpoint is pathological response after the single neoadjuvant dose, with secondary analyses of efficacy, safety, and biomarker discovery.

Who should consider this trial

Good fit: Adults (≥18) with biopsy-proven primary cutaneous melanoma Stage IIb/c (Breslow >2.0 mm with ulceration or >4.0 mm without ulceration), measurable primary lesion not fully removed by diagnostic biopsy, ECOG 0-1, adequate organ function, and planned for wide local excision with sentinel lymph node biopsy.

Not a fit: Patients with clinically evident lymph-node or distant metastatic disease, thin melanomas below the Stage IIb/c thresholds, poor organ function, or those who cannot delay surgery for four weeks are unlikely to benefit from this neoadjuvant approach.

Why it matters

Potential benefit: If successful, a single pre-surgery dose could stimulate an anti-tumor immune response that reduces the chance of recurrence and helps guide further treatment decisions.

How similar studies have performed: Other neoadjuvant PD-1 inhibitor trials in melanoma have shown promising pathological responses, although single-dose, placebo-controlled data remain limited.

Eligibility criteria

Inclusion Criteria:

1. Patient is ≥18 years.
2. Signed informed consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
4. Histopathologically confirmed primary cutaneous melanoma stage IIb/c (Breslow \>2.0 mm with ulceration OR Breslow \>4.0mm without ulceration) with a minimum diameter of 5 mm not completely removed by the diagnostic biopsy
5. Patient planned for wide local excision and sentinel lymph node biopsy
6. Adequate organ function on blood test
7. 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.
8. Female patients of childbearing potential must be willing to use an adequate 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.
9. 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.

Exclusion Criteria:

1. Life expectancy of less than 3 years.
2. Patients who are unable to undergo general anesthesia for any reason.
3. Clinical or radiographic evidence of nodal, satellite, in-transit or distant metastases
4. Risk for developing in-operable disease due to study procedures as judged by study investigator
5. Prior immunotherapy for any malignancy
6. Use of live vaccines four weeks before or after the last study treatment.
7. History of severe reactions to monoclonal antibodies.
8. Active autoimmune disease or a documented history of autoimmune disease requiring systemic immunomodulatory treatment. Diabetes, rheumatoid arthritis, psoriasis, atopic dermatitis and hypothyroidism are excepted.
9. 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.
10. Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs.
11. Has a known additional malignancy that is progressing or requires active treatment.
12. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study drug.
13. A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate in the opinion of the treating investigator.

Where this trial is running

Gothenburg

• Sahlgrenska University Hospital — Gothenburg, Sweden (Recruiting)

Study contacts

• Study coordinator: Roger Olofsson Bagge, Professor

Conditions Melanoma; IMMUNOTHERAPY; PRIMARY CUTANOUS MELANOMA; NEOPRIME trial; NEOADJUVANT TREATMENT