PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients
ConditionMelanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGrupo Español Multidisciplinar de Melanoma
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of unresectable or metastatic melanoma will be enrolled in this study.
Participants must have measurable disease by investigator assessment according to RECIST v1.1 Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy.
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3. OR
WOCBP should remain on contraception for 12 months after the last dose of EV or 4 months after pembrolizumab, whichever occurs last.
Disqualifiers
Participants who have previously received enfortumab vedotin or other MMAE-based ADCs.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the scheduled date of starting the study treatment.
Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
Trial design
Design model
Parallel
Treatments tested in this trial
enfortumab vedotin
DrugEnfortumab vedotin 1.25 mg/kg be administered on Days 1,8,22 and 29 of every 6-week cycle by IV infusion given over approximately 30 minutes.
pembrolizumab
DrugPembrolizumab 400 mg on day 1 of each 42-day cycle (Q6W)
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Cohort 1Experimental treatment 2 interventions
Group B: Cohort 2Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Objective response rate (ORR)
Objective Response Rate (ORR) as assessed by the investigator through Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). This will be considered as the percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the study. Estimates of the ORR along with the associated 95% exact binomial confidence intervals will be provided. The binomial probability that the observed melanoma ORR is \> 0.15 will be calculated. Best confirmed response will be summarized. Response of melanoma will be measured by CT or MRI and assessed according to RECIST 1.1 by the investigator. If there are no assessments, the response will be taken to be unconfirmed and a non-response. Changes in tumor size from baseline will be calculated and displayed graphically, where appropriate.
Time frame
Throughout the study period,period, from initiation of treatment up to 2 yearsSecondary outcomes
1
Progression-free Survival (PFS) 6 months
Progression-free Survival (PFS) defined as the time from the start of treatment to disease progression or death from any cause, whichever occurs first. The PFS will be estimated by the Kaplan-Meier method. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without event will be censored on the date of first dose of the subsequent anticancer treatment. PFS will be displayed graphically where appropriate. PFS will be assessed by the median / mean (95% CI) and for different timepoints: Proportion of patients without progression at the end of follow-up. Proportion of patients at 6-months, 12-months and as deemed opportune by the time of the analysis. Confidence intervals (CIs) for the 25th, 50th and 75th percentiles will be reported. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable.
Time frame
Throughout the study period, from initiation of treatment up to 6 months2
Progression-free Survival (PFS) 12 months
Progression-free Survival (PFS) defined as the time from the start of treatment to disease progression or death from any cause, whichever occurs first. The PFS will be estimated by the Kaplan-Meier method. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without event will be censored on the date of first dose of the subsequent anticancer treatment. PFS will be displayed graphically where appropriate. PFS will be assessed by the median / mean (95% CI) and for different timepoints: Proportion of patients without progression at the end of follow-up. Proportion of patients at 6-months, 12-months and as deemed opportune by the time of the analysis. Confidence intervals (CIs) for the 25th, 50th and 75th percentiles will be reported. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable.
Time frame
Throughout the study period, from initiation of treatment up to 12 months3
Overall survival (OS)
Overall survival (OS): defined as the time elapsed from the first dose of study treatment until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact. OS will be summarized using the Kaplan-Meier method and displayed graphically where appropriate. Confidence intervals (CIs) for the 25th, 50th and 75th percentiles will be reported. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable. OS will be calculated as median / mean (95% CI) and OS rate for different timepoints deemed appropriate at the time of the analysis (i.e.1-year OS rate) will also be calculated.
Time frame
Throughout the study period, from initiation of treatment up to 12 months4
Overall survival (OS)
Overall survival (OS): defined as the time elapsed from the first dose of study treatment until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact. OS will be summarized using the Kaplan-Meier method and displayed graphically where appropriate. Confidence intervals (CIs) for the 25th, 50th and 75th percentiles will be reported. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable. OS will be calculated as median / mean (95% CI) and OS rate for different timepoints deemed appropriate at the time of the analysis (i.e.1-year OS rate) will also be calculated.
Time frame
Throughout the study period, from initiation of treatment up to 24 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Grupo Español Multidisciplinar de Melanoma
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
Astellas Pharma Inc
Collaborator
Source ClinicalTrials.gov