Advanced melanoma (unresectable or metastatic) MedDRA version: 14.1 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: SCH 900475
MK-3475
Pharmaceutical Form: Powder for injection
INN or Proposed INN: ambrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: SCH 9
MK-3475
Other descriptive name: Anti-PD-1 monoclonal antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Patient must have a histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic MEL not amenable to local therapy. ?Patient may not have a diagnosis of uveal melanoma. 2)Patiens must be refractory to ipilimumab, defined as: ?Received at least two doses of ipilimumab ?Documented disease progression within 24 weeks of the last dose of ipilimumab. Patients who were re-treated with ipilimumab and patients who were on maintenance ipilimumab will be allowed to enter the trial as long as there is documented PD within 24 weeks of the last treatment date (with ipilimumab). ?Progressive disease will be defined as increase in tumor burden >25% relative to nadir (minimum recorded tumor burden) which is confirmed by repeat assessment (investigator determination based on site radiology reading; SPONSOR will collect CT scans for retrospective analysis) no less than four weeks from the date of the first documented PD. Once PD is confirmed, initial date of PD documentation will be considered as the date of disease progression. 3)Full resolution of ipilimumab related AEs (including irAEs) back to baseline and off steroid treatment for irAEs for at least two weeks. 4)Full resolution of ipilimumab related AEs (including irAEs) back to baseline and off of steroid treatment (>10 mg/day prednisone or equivalent dose) for irAEs for at least two weeks prior to first dose of study drug. ?No history of severe irAEs from ipilimumab CTCAE Grade 4 requiring steroid treatment; CTCAE Grade 3 requiring steroid treatment (>10 mg/day prednisone or equivalent dose) >12 weeks ?Minimum of four weeks (wash out period) from the last dose of ipilimumab 5)Patients must consent to allow correlative studies and should have available tumor tissue (formalin fixed paraffin embedded block or unstained slides). These tumor tissues could be archival or fresh tumor biopsy as part of this trial. 6)Patients with BRAF V600E mutant melanoma must have also been previously treated with a BRAF and/or MEK inhibitor. Patient must have progressive disease after the most recent treatment regimen. 7)Patient must have measurable disease as per RECIST version 1.1 (Appendix 6.1) Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1)Patient who has had chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or who has not recovered to CTCAE Grade 1 or better from the AEs due to cancer therapeutics administered more than four weeks earlier. ?The requirements for prior ipilimumab treatment are listed in Inclusion Criterion 2. 2)Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug. 3)Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Overall Response Rate by Week 12; Progression-Free Survival; Overall Survival;Timepoint(s) of evaluation of this end point: Overall Response Rate by Week 12; Progression-Free Survival; Overall Survival; Main Objective: 1)To evaluate the overall response rate (ORR) by Week 12 in patients with ipilimumab refractory advanced MEL receiving either MK-3475 or chemotherapy. Hypothesis: Administration of MK-3475 will result in a clinically meaningful improvement in ORR versus treatment with chemotherapy. 2)To evaluate the progression-free-survival (PFS) in patients with ipilimumab refractory advanced MEL receiving either MK-3475 or chemotherapy. Hypothesis: Administration of MK-3475 will result in a clinically meaningful improvement in PFS versus treatment with chemotherapy. 3)To evaluate the overall survival (OS) in patients with ipilimumab refractory advanced MEL receiving either MK-3475 or chemotherapy. Hypothesis: Administration of MK-3475 will result in a clinically meaningful improvement in OS versus treatment with chemotherapy. ; Secondary Objective: 1)To further characterize the PK profile of single agent MK-3475 at 2 mg/kg and 10 mg/kg. 2)To evaluate safety, tolerability and adverse experience profile of single agent MK-3475 2 mg/kg and 10 mg/kg. 3)To evaluate response duration, OS at Week 12 and DCR by Week 12 of ipilimumab refractory MEL patients who are treated with MK-3475 or chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Response Duration; Disease control rate by Week 12; Overall Survival Rate at Week 12.;Timepoint(s) of evaluation of this end point: Response Duration; Disease control rate by Week 12; Overall Survival Rate at Week 12. | — |
Countries
Argentina, Australia, France, Germany, Israel, Italy, Netherlands, Norway, Spain, Sweden, United States
Contacts
Public ContactMarta Arias-Salgado Ruiz-Gimenez
Merck Sharp & Dohme de España S.A
Outcome results
None listed