Short versus long immunotherapy after radical surgery for high-risk malignant melanoma

A Prospective Randomized International Multicenter Study to Compare Short Versus Long Adjuvant Immunotherapy After Radical Surgery of Stage IIb-c, III and IV Cutaneous Malignant Melanoma (Grand SLAM)

This will test whether six months of immunotherapy works as well as the standard 12 months for adults who have had surgery for high-risk melanoma.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1792 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Uppsala University (Academic / other)
• Drugs / interventions: pembrolizumab, nivolumab, immunotherapy, radiation, prednisone, relatlimab, fianlimab, cemiplimab, vibostolimab
• Locations: 26 sites (Helsinki and 25 other locations)
• Trial ID: NCT06488482 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, international phase 3 study comparing a shorter (six-month) versus standard (twelve-month) course of adjuvant PD-1 immunotherapy (nivolumab or pembrolizumab) after radical surgery for stage IIb-c, III, and IV cutaneous malignant melanoma. Eligible adults with ECOG 0-1 and adequate organ function are randomized at participating centers and followed for recurrence and safety outcomes. Neoadjuvant immunotherapy is allowed in some cases if a complete pathological response was not achieved. The trial aims to determine whether the shorter regimen preserves efficacy while reducing severe toxicity, visit burden, and drug costs.

Who should consider this trial

Good fit: Adults (≥18 years) with stage IIb-c, III, or IV cutaneous malignant melanoma who have had radical surgery, have ECOG 0-1, and meet standard organ-function requirements for immunotherapy are the intended participants.

Not a fit: Patients with ongoing progressive disease after neoadjuvant therapy, inadequate organ function, or those with lower-stage melanoma not meeting eligibility are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, a six-month regimen could provide the same protection against recurrence with fewer severe side effects, fewer hospital visits, and lower treatment costs.

How similar studies have performed: Previous adjuvant trials have shown that 12 months of PD-1 therapy reduces recurrence risk, but no randomized trial has yet proven that a six-month regimen is equally effective.

Eligibility criteria

Inclusion Criteria:

1. Provision of written informed consent for participation.
2. ≥ 18 years of age.
3. Performance status ECOG/WHO 0-1.
4. Adequate organ functions as per standards for immunotherapy.
5. Radical surgery for CMM (including acral) stage IIb-c, III (including in transit) and IV. Stage III CMM patients with unknown primary and stage IIb-c CMM patients who have not undergone sentinel node procedure are eligible.
6. A complete physical examination within 28 days prior to randomization
7. Previous adjuvant treatment with BRAF + MEK inhibitors is allowed.
8. Neoadjuvant treatment with immunotherapy for two months (currently pembrolizumab every third weeks three times or nivolumab every fourth week two times) is allowed providing that a complete or near complete pathological response was not achieved and patients with clear progressive disease according to the pathology report are not eligible.
9. All participants who have not received neo-adjuvant treatment must have disease-free status documented by radiological assessment within 28 days prior to randomization while 6 weeks is sufficient for neo-adjuvant treated patients.
10. Participants must be off immunosuppressive doses of systemic steroids (\>10 mg/day prednisone or equivalent) for a minimum of 14 days prior to study drug administration.
11. Sufficient renal function for radiological assessments with i.v. contrast.
12. Peri-operative radiation therapy is allowed.
13. Patients who experience a locoregional lymph node relapse, i.e. stage III disease or operable stage IV at a time-point later than primary diagnosis are welcome to participate.

Exclusion Criteria:

1. The patient is, in the opinion of the investigator, assessed as unfit to receive systemic adjuvant treatment.
2. Serious and/or uncontrolled medical disorder that in the opinion of the investigator is contraindicated.
3. An active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism requiring hormone replacement only and skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are eligible.
4. Life-expectancy less than 2 years due to concurrent disease (e.g., cardiac disease and liver cirrhosis).
5. Inability to provide informed consent or refusal to do so.
6. Inability to comply with the study protocol.
7. Participation in other clinical trials interfering with the current study protocol.
8. Existing or previous malignancies within the past 5 years (except for in situ breast and in situ cervical cancer, melanoma in situ, malignant melanoma, non-melanoma skin cancer and low risk prostate cancer).
9. Pregnancy or planned pregnancy.
10. Ocular and mucosal melanoma.

Where this trial is running

Helsinki and 25 other locations

• Helsinki University Hospital — Helsinki, Finland (Recruiting)
• Kuopio University Hospital — Kuopio, Finland (Recruiting)
• Tampere University Hospital — Tampere, Finland (Recruiting)
• Turku University Hospital — Turku, Finland (Recruiting)
• Ålesund Hospital — Ålesund, Norway (Recruiting)
• Haukeland University Hospital — Bergen, Norway (Recruiting)
• Sorlandet Hospital — Kristiansand, Norway (Recruiting)
• Akershus University Hospital — Oslo, Norway (Recruiting)
• Oslo University Hospital — Oslo, Norway (Recruiting)
• Stavanger University Hospital — Stavanger, Norway (Recruiting)
• North Norway University Hospital — Tromsø, Norway (Recruiting)
• Trondheim University Hospital — Trondheim, Norway (Recruiting)
• Eskilstuna Hospital — Eskilstuna, Sweden (Recruiting)
• Falu Hospital — Falun, Sweden (Recruiting)
• Gävle Hospital — Gävle, Sweden (Recruiting)
• Sahlgrenska University Hospital — Gothenburg, Sweden (Recruiting)
• Ryhov Hospital — Jönköping, Sweden (Recruiting)
• Kalmar Hospital — Kalmar, Sweden (Recruiting)
• Karlstad Hospital — Karlstad, Sweden (Recruiting)
• Linköping University Hospital — Linköping, Sweden (Recruiting)
• Skåne University Hospital — Lund, Sweden (Recruiting)
• Örebro University Hospital — Örebro, Sweden (Recruiting)
• Karolinska University Hospital — Stockholm, Sweden (Recruiting)
• Sundsvall Hospital — Sundsvall, Sweden (Recruiting)
• Växjö Hospital — Vaxjo, Sweden (Recruiting)
• Västmanland Hospital — Västerås, Sweden (Recruiting)

Study contacts

• Principal investigator: Gustav J Ullenhag, professor — Uppsala University Hospital
• Study coordinator: Gustav J Ullenhag, professor

Conditions High-risk Melanoma