cancer Melanoma
Conditions
Interventions
Talimogene laherparepvec, Amgen Investigational Product Dosage and
Administration:
Talimogene laherparepvec will be administered by intralesional injection only
into injectable cutaneous, subcutaneo
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Male or female age >= 18 years with histologically confirmed diagnosis of melanoma, and with a disease stage IIIB, IIIC, IIID, IVM1a, IVM1b, IVM1c or Stage IVM1d (with up to 3 cerebral metastases, provided that all lesions have been adequately treated). Subject must be a candidate for intralesional therapy into cutaneous, subcutaneous, or nodal melanoma lesion. Subjects must have ECOG performance status of 0 or 1 and must have measurable disease, and adequate organ function as determined by hematological, renal, hepatic and coagulation laboratory criteria - Subject must have recovered from all adverse events, due to prior anticancer therapy, and, if subject received major surgery, must have recovered adequately from toxicity and/or complications prior to enrollment. Subject must have had prior treatment with a PD-1 inhibitor in the adjuvant or metastatic setting, and must have received prior anti-PD-1 therapy for at least 2 to 3 consecutive cycles within an 8 week period. The anti-PD-1 therapy must be the immediate prior line of therapy before enrollment. Subject must 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. - Subjects will be enrolled into 1 of 4 cohorts based on prior anti-PD-1 experience: o Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance: subject received anti-PD1 therapy in the locally recurrent/metastatic setting and experienced a best overall response of disease progression or stable disease prior to confirmed disease progression. The initial date of disease progression must occur within 12 weeks of the last dose of a PD-1 inhibitor. OR o Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance: subject received anti-PD-1 therapy in the locally recurrent/metastatic setting and experienced confirmed disease progression following a complete or partial response on anti-PD-1 therapy per investigator assessment. The initial date of disease progression must occur within 12 weeks of the last dose of a PD-1 inhibitor. OR o Cohort 3 - Adjuvant Setting - Disease Free Interval = 6 months: subject received anti PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease free interval of >= 6 months after starting the adjuvant PD-1 inhibitor. - For a full list of eligibility criteria please refer to Section 6.1 of the protocol.
Exclusion criteria
Exclusion criteria: - Subject must not have rapid clinical progression due to melanoma, considered by the investigator, or stage IVM1d with greater than 3 cerebral melanoma metastases, or clinically active cerebral melanoma metastases requiring therapy and/or carcinomatous meningitis regardless of clinical stability - Subject must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states or history of other malignancy within the past 3 years with the exceptions of the prior malignancies noted in Section 6.2 of the protocol. - Subject must not have 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 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, known human immunodeficiency virus (HIV) disease, known acute or chronic hepatitis B or hepatitis C infection, a known history of active Bacillus tuberculosis or a has a history of (non-infectious) pneumonitis. Subject must not have undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. - Subject must not have received prior therapy with talimogene laherparepvec or any other oncolytic viruses, prior therapy with tumor vaccine (unless administered in the adjuvant setting), prior systemic anti-cancer therapy (including investigational agents) within 28 days prior to enrollment or prior radiotherapy within 14 days of enrollment - For a full list of eligibility criteria please refer to Section 6.2 of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response (complete response [CR] + partial response [PR]) (by investigator assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| - Complete respons, BOR, durable respons, DOR, and disease control, (investigator assessment using modified RECIST v1.1 and modified irRC-RECIST (immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors)) and overall response using modified irRC-RECIST by investigator assessment. - PFS (by investigator assessment using modified RECIST v1.1 and modified irRC-RECIST) - OS | — |
Countries
Netherlands
Outcome results
None listed