Actively Recruiting
PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients
Led by Grupo Español Multidisciplinar de Melanoma · Updated on 2025-09-18
60
Participants Needed
13
Research Sites
155 weeks
Total Duration
On this page
Sponsors
G
Grupo Español Multidisciplinar de Melanoma
Lead Sponsor
M
Merck Sharp & Dohme LLC
Collaborating Sponsor
AI-Summary
What this Trial Is About
There is a lack of strategies for patients who progress after responding to PD-1/l-1 in melanoma. High expression of Nectin4 in skin and melanomas may serve as a new target in advanced melanomas. The combination of enfortumab/vedotin (EV) and pembrolizumab has shown synergistic effect in various solid tumors. Enfortumab vedotin and pembrolizumab may have a dual effect on clinical outcomes. PLUGIN is a multicenter, non-randomized open-label, 2-cohort, phase 2 study to evaluate the ORR of pembrolizumab in combination with enfortumab vedotin (EV) in previously treated participants with unresectable stage III or IV melanoma and disease progression on standard therapy. The primary objective is evaluate the efficacy of enfortumab/vedotin and pembrolizumabplus pembrolizumab in advanced melanoma. Hypothesis: 1) High expression of Nectin4 in skin and melanomas may serve as a new target in advanced melanomas; 2)EV+Pembrolizumab has shown synergistic effect in various solid tumors; 3) There is a lack of strategies for patients who respond to PD1-mAbs in melanoma. Primary Endpoint: Objective Response Rate (ORR) as assessed by the investigator according RECIST 1.1 A total of 60 patients will be enrolled in this study to evaluate efficacy and outcomes in two different cohorts: Cohort 1: patients who did not have BRAF mutation V600E and had disease progression on immune (IO) therapy. Cohort 2, patients with activating BRAF mutations, must have progressed on IO therapy and BRAF/MEKi
CONDITIONS
Official Title
PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male or female participants aged 18 years or older with histologically confirmed unresectable or metastatic melanoma
- Measurable disease by RECIST v1.1 assessment
- Male participants must agree to use contraception during treatment and for 9 months after last enfortumab vedotin dose or 4 months after pembrolizumab, whichever is later
- Female participants must not be pregnant or breastfeeding and either not be women of childbearing potential or agree to use contraception for 12 months after last enfortumab vedotin dose or 4 months after pembrolizumab, whichever is later
- Participants must have progressed on anti-PD-1/L1 therapy after receiving at least two doses
- BRAF mutated patients must have received BRAF/MEK inhibitors and PD1/PDL1 therapy
- Participants must have recovered from prior therapy toxicities to Grade 1 or baseline (with exceptions for endocrine AEs and neuropathy Grade 2 or lower)
- Provide archival or fresh tumor tissue sample after last treatment progression
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Adequate organ function as defined in the study protocol
You will not qualify if you...
- Positive pregnancy test for women of childbearing potential within 72 hours prior to enrollment
- Previous treatment with enfortumab vedotin or other MMAE-based antibody-drug conjugates
- Prior systemic anti-cancer therapy within 4 weeks before study treatment
- Prior radiotherapy within 2 weeks before study treatment or radiation-related toxicities needing corticosteroids
- Live or live-attenuated vaccine received within 30 days before study treatment
- Investigational agent or device use within 4 weeks before study treatment
- Uncontrolled diabetes defined as HbA1c ≥8% or HbA1c 7% to <8% with associated symptoms
- Immunodeficiency or recent immunosuppressive therapy exceeding 10 mg prednisone daily within 7 days before treatment
- Active or progressing additional malignancy within past 2 years (except certain skin cancers and carcinoma in situ)
- Active central nervous system metastases or carcinomatous meningitis
- Severe hypersensitivity (Grade 3 or higher) to pembrolizumab or enfortumab vedotin excipients
- Active keratitis or corneal ulcerations (superficial punctate keratitis allowed if treated)
- Active autoimmune disease requiring systemic treatment in past 2 years (except hormone replacement)
- Systemic corticosteroid use over 10 mg prednisone daily or other immunosuppressive medications
- History or current pneumonitis or interstitial lung disease requiring corticosteroids
- Active infection needing systemic therapy
- Known HIV infection
- Active hepatitis B or C infection
- Incomplete recovery from major surgery or ongoing complications
- Psychiatric or substance abuse disorders interfering with study participation
- Pregnant, breastfeeding, or planning to conceive/father children during contraception period
- History of allogenic tissue or solid organ transplant
- History of clinical tuberculosis
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 13 locations
1
Complexo Hospitalario Universitario de A Coruña
A Coruña, A Coruña, Spain, 15006
Actively Recruiting
2
Institut Català D'Oncologia - Badalona
Badalona, Barcelona, Spain, 08916
Actively Recruiting
3
Hospital Universitari Dexeus
Barcelona, Barcelona, Spain, 08028
Not Yet Recruiting
4
Hospital Universitario Valle de Hebrón
Barcelona, Barcelona, Spain, 08035
Actively Recruiting
5
Hospital Clinic de Barcelona
Barcelona, Barcelona, Spain, 08036
Actively Recruiting
6
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain, 39008
Actively Recruiting
7
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Spain, 28034
Actively Recruiting
8
Hospital Universitario 12 de Octubre
Madrid, Madrid, Spain, 28041
Actively Recruiting
9
Hospital Universitario La Paz
Madrid, Madrid, Spain, 28046
Actively Recruiting
10
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, Murcia, Spain, 30120
Actively Recruiting
11
Hospital Virgen del Rocío
Seville, Sevilla, Spain, 41013
Actively Recruiting
12
Hospital General de Valencia
Valencia, Valencia, Spain, 46014
Actively Recruiting
13
Hospital Universitario Miguel Servet
Zaragoza, Zaragoza, Spain, 50009
Actively Recruiting
Research Team
A
A responsible person designated by the sponsor, M.D., PhD.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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