Neoadjuvant pembrolizumab in patients with stage IIb/c melanoma, a phase II double-blind placebo-controlled randomized trial NEOPRIME

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-06-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To measure the pathological response to one dose of pembrolizumab 400 mg before surgery in patients with AJCC stage IIB or IIC melanoma

Secondary objectives 15

1. To describe the safety and tolerability of neoadjuvant and surgical procedures.
2. To assess the feasibility of conducting a neoadjuvant study in this patient population
3. To determine the positive sentinel node biopsy rate at surgery
4. To assess local recurrence rate
5. To assess regional recurrence rate
6. To assess event free survival (EFS).
7. To assess recurrence free survival (RFS).
8. To assess distant metastasis-free survival (DMFS).
9. To assess melanoma specific survival (MSS).
10. To assess overall survival (OS).
11. To assess any change in dermoscopy images during neoadjuvant treatment.
12. To assess any change in melanoma thickness as assessed with HFUS during neoadjuvant treatment.
13. To assess change in ctDNA levels during and after neoadjuvant treatment and surgery
14. To assess change in T-cell receptor repertoire before and after neoadjuvant treatment
15. Predictive and prognostic biomarker discovery

Conditions and MedDRA coding

Stage IIb/c melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 13

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathological response rate

Secondary endpoints 14

1. Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
2. Feasibility of neoadjuvant therapy in stage II melanoma
3. Sentinel lymph node positivity rate
4. Local recurrence rate
5. Regional recurrence rate
6. Recurrence-free survival (RFS)
7. Distant-metastasis free survival
8. Melanoma-specific survival (MSS)
9. Overall survival (OS)
10. Change in dermoscopic features and correlation to histopathology
11. Change in tumor thickness as assessed with ultrasound and correlation to histopathology
12. Change in ctDNA levels during and after neoadjuvant treatment and surgery
13. Change in T-cell receptor repertoire before and after neoadjuvant treatment
14. Predictive and prognostic biomarker discovery

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Roger Olofsson Bagge

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Roger Olofsson Bagge

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

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