Previously Untreated, Unresected, Stage IIIB to IVM1c Melanoma MedDRA version: 17.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1b and Part 1 of Phase 2: Male or female age = 18 years with histologically confirmed diagnosis of melanoma and stage IIIB to IVM1c for whom surgery in not recommended. Subject must be treatment naïve (ie, must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IVM1c melanoma. Subject who received prior adjuvant therapy for melanoma will not be excluded (including, but not limited to, interferon, limb infusion/perfusion, or use of investigational agents in the adjuvant setting). However, if the subject received adjuvant therapy, the subject must have completed therapy at least 6 months prior to enrollment. Subject must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate hematologic, hepatic, renal, and coagulation function. Part 2 of Phase 2: Subject randomized to arm 2 (MK-3475 monotherapy arm) of part 1 of the phase 2 study must have evidence of PD at week 12 or subsequent tumor assessment visit through month 20 documented by an independent central review committee and confirmed by the investigator = 4 weeks later using modified irRC. Subject must have ECOG performance status of 0 or 1, and adequate hematologic, hepatic, renal, and coagulation function 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 57 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 53
Exclusion criteria
Exclusion criteria: Phase 1b and Part 1 of Phase 2: Subject must not have clinically active cerebral metastases. Subject with up to 3 cerebral metastases, and neurological performance status of 0 may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or gammaknife therapy, with no evidence of progression, and have not required steroids, for at least 2 months prior to enrollment. Subject 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 of the prior malignancies. Subject must not have received prior talimogene laherparepvec, tumor vaccine, MK-3475, other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, ipilimumab, other cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, even if given in the adjuvant setting. Subject must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, other symptomatic autoimmune disease, documented history of autoimmune disease or syndrome requiring systemic steroids or immunosuppressive agents (except vitiligo or resolved childhood asthma/atopy), or evidence of clinically significant immunosuppression. Subject 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. Part 2 of Phase 2: Subject must not have stopped MK-3475 treatment in part 1 of phase 2 due to intolerance or reasons other than confirmed PD per modified irRC at week 12 or subsequent tumor assessment visit through month 20. Subject must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, other symptomatic autoimmune disease, documented history of autoimmune disease or syndrome requiring systemic steroids or immunosuppressive agents (except vitiligo or resolved childhood asthma/atopy), or evidence of clinically significant immunosuppression. Subject 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: Phase 1b: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with MK-3475 in subjects with previously untreated, unresected, stage IIIB to IVM1c melanoma. Phase 2, Part 1: To evaluate the efficacy, as assessed by the confirmed objective response rate (ORR) by week 24 of treatment with talimogene laherparepvec in combination with MK-3475, as compared to MK-3475 alone. Phase 2, Part 2: To evaluate the efficacy, as assessed by the confirmed ORR by week 24 of treatment with talimogene laherparepvec in combination with MK-3475 following progression on MK-3475 alone in part 1 of phase 2.;Secondary Objective: Dependent on phase of study: -efficacy of talimogene laherparepvec in combination with MK-3475; as compared to MK-3475 alone; as compared to MK-3475 alone in subjects who are either PD-L1-negative or -positive prior to initiating therapy; or confirmed PD on MK-3475 -safety of talimogene laherparepvec in combination with MK-3475; compared to MK-3475 alone; or following confirmed PD on MK-3475 alone -incidence of anti-MK-3475 antibodies when MK-3475 is administered in combination with talimogene laherparepvec; alone or in combination with TVEC; or following confirmed PD on MK-3475 alone -PK of MK-3475 when administered in combination with TVEC; or in combination with talimogene laherparepvec; or following confirmed PD on MK-3475 alone -whether talimogene laherparepvec induces changes in PD-L1 expression by immunohistochemistry in injected and in non-injected lesions;Primary end point(s): Phase 1b: • Incidence of DLT Phase 2, Part 1: • Confirmed ORR (CR+PR) by week 24 from the date of the first dose of MK-3475 in phase 2 part 1 (response evaluation by an investigator using modified immune-related Response Criteria [irRC]) Phase 2, Part 2: • Confirmed ORR (CR+PR) by week 24 from the date of the first dose of MK-3475 in combination with talimogene laherparepvec in phase 2 part 2 ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b: • Confirmed ORR (CR+PR) by 24 weeks from the date of the first dose of MK-3475. • BOR, DRR, DOR, PFS, and OS • Ordinal categorical response score • Incidence of treatment-emergent and treatment-related adverse events (all AEs, grade = 3 AEs, serious adverse events, fatal AEs, and AEs defined as events of interest). • Incidence of anti-MK-3475 antibodies • Descriptive statistics of trough and peak levels of MK-3475 Phase 2, Part 1: • BOR, DRR, DOR, PFS, and OS • Ordinal categorical response score and deep response rate (CR+Very Good Partial Response [VGPR]) • BOR, ordinal categorical response score, deep response rate, (CR+VGPR), DRR, DOR, PFS, and OS for PD-L1 negative subjects and PD-L1 positive subjects based on pre-treatment biopsy specimen. • Incidence of treatment-emergent and treatment-related adverse events (all AEs, grade = 3 AEs, serious adverse events, fatal AEs, and AEs defined as events of interest. • Incidence of anti-MK-3475 antibodies. • Descriptive statistics of trough and peak levels of MK-3475. Phase 2, Part 2: • BOR, ordinal categorical response score, deep response rate (CR+VGPR), DRR, DOR, PFS and OS. • Incidence of treatment-emergent and treatment-related adverse events (all AEs, grade = 3 AEs, serious adverse events, fatal AEs, and AEs defined as events of interest). • Incidence of anti-MK-3475 antibodies. • Pharmacokinetic parameters for MK-3475. Phase 1b and Phase 2: • Changes in PD-L1 expression by immunohistochemistry (eg, negative to positive) that occur in injected lesions after starting talimogene laherparepvec in either subjects who are treatment-naïve (phase 1b) or those who have been receiving MK-3475 (part 2 of phase 2) and are PD-L1-negative prior to receiving talimogene laherparepvec. • Changes in PD-L1 expression by immunohistochemistry (eg, negative to positive) that occur in non-injected lesions after starting talimogene laherparepvec in either subjects who are treatment | — |
Countries
Australia, Austria, Belgium, Czech Republic, Finland, Germany, Greece, Hungary, Italy, Portugal, Spain, Sweden, Switzerland, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed