Unresectable/Metastatic Stage IIIB-IVM1d Melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: This study will enroll subjects -who are male or female age > 18 years at the time of informed consent -with histologically confirmed diagnosis of melanoma (unresectable or metastatic stage IIIB, IIIC, IIID, IVM1a, IVM1b, IVM1c, or IVM1d melanoma). - Subjects with stage IVM1d and up to 3 cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or gamma knife therapy, with no evidence of progression and not requiring steroids for at least 2 months prior to enrollment. -Subjects must have measurable disease and be a candidate for intralesional therapy. -Subjects must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 -Adequate hematologic, hepatic, renal, and coagulation function. - Subject must also have received prior anti-PD-1 therapy for at least 2 to 3 consecutive cycles within an 8 week period and have disease progression as defined by RECIST v1.1 criteria. Note: subjects with prior treatment and disease progression on more than 1 line of anti-PD-1 therapy are excluded. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: -Subjects must not have clinically active cerebral melanoma metastases and/or carcinomatous meningitis. -Subjects must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia), or history of other malignancy within the past 3 years with the exceptions noted in Section 6.2 of the protocol. -Subjects must not have been previously treated with talimogene laherparepvec, any other oncolytic viruses, or tumor vaccine (unless administered in the adjuvant setting). -Subjects must not have a history or evidence of symptomatic autoimmune glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. -Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. -Subjects must not have active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Talimogene laherparepvec in combination with pembrolizumab as assessed by objective response rate (ORR) in subjects with unresectable/metastatic stage IIIB-IVM1d melanoma who have progressed on prior anti-PD-1 therapy;Secondary Objective: -To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by: o Complete response rate (CRR), best overall response, (BOR) durable response rate, (DRR) duration of response, (DOR) and disease control rate, (DCR) o ORR using modified irRC-RECIST o Progression free survival (PFS) o Overall survival (OS) -To evaluate the safety of talimogene laherparepvec in combination with pembrolizumab as assessed by incidence of treatment-emergent and treatment-related adverse events, and abnormal laboratory tests in patients who have progressed on prior anti-PD-1 therapy -To evaluate time to subsequent anti-cancer therapy;Primary end point(s): Overall response (complete response [CR]+partial response [PR]) (by investigator assessment using modified Response Evaluation Criteria in Solid Tumor [RECIST v1.1]);Timepoint(s) of evaluation of this end point: - Efficacy analysis will be performed on the Full Analysis Set (FAS) defined as all enrolled subjects who received at least 1 dose of talimogene laherparepvec and at least 1 dose of pembrolizumab in combination and the Per Protocol Analysis Set (PPAS). The PPAS is a subset of the FAS and includes subjects who do not have important protocol deviations that are considered to have an impact on efficacy outcomes. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Complete response, BOR, durable response, DOR, and disease control, (investigator assessment using modified RECIST v1.1 and modified irRC-RECIST) and overall response using modified irRC-RECIST by investigator assessment -PFS (by investigator assessment using modified RECIST v1.1 and modified irRC-RECIST) -OS -Incidence of treatment-emergent and treatment-related adverse events (all adverse events, grade = 3 adverse events, serious adverse events, fatal adverse events, adverse events defined as events of interest), and abnormal laboratory tests -Time to subsequent anti-cancer therapy;Timepoint(s) of evaluation of this end point: - Efficacy analysis will be performed on the Full Analysis Set (FAS) defined as all enrolled subjects who received at least 1 dose of talimogene laherparepvec and at least 1 dose of pembrolizumab in combination and the Per Protocol Analysis Set (PPAS). The PPAS is a subset of the FAS and includes subjects who do not have important protocol deviations that are considered to have an impact on efficacy outcomes. - The Safety Analysis Set (SAS), defined as all enrolled subjects who received at least 1 dose of talimogene laherparepvec or pembrolizumab, will be used in the analysis of the safety endpoints. | — |
Countries
France, Germany, Greece, Italy, Netherlands, Poland, Spain, United Kingdom
Contacts
Public ContactMedical Information
Amgen Biotechnologia Sp. z o.o.
Outcome results
None listed