Patients with early metastatic (stage IIIB/C/D/IV M1a (AJCC 8)) melanoma MedDRA version: 21.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: SOC Class
Conditions
Interventions
Trade Name: Opdivo
Product Name: Nivolumab
Pharmaceutical Form: Solution for injection/infusion
Trade Name: Imlygic
Product Name: Talimogene Laherparepvec
Product Code: AMG 678
Pharmaceutical Form: S
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adults at least 18 years of age - WHO performance score of 0 or 1 - Cytologically or histologically confirmed diagnosis of stage IIIB/C/D/IVM1a (AJCC 8th edition) melanoma, eligible for surgical resection. - Subjects must have measurable disease according to RECIST 1.1 and must be a candidate for intralesional therapy with at least one injectable cutaneous, subcutane-ous or nodal melanoma lesion (= 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of = 10 mm. - Prior isolated limb perfusion (ILP) is allowed (= 12 weeks prior to enrollment) - Screening laboratory values must meet the following criteria: - WBC = 2.0x10^9/L, Neutrophils =1.5x10^9/L, Platelets =100 x10^9/L, Hemoglobin =5.5 mmol/L, Creatinine =1.5x ULN, AST = 1.5 x ULN, ALT = 1.5 x ULN, Bilirubin =1.5 X ULN - LDH =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: - Liver, Bone, Lung, Brain or other Visceral Metastases. - No measurable lesion according to RECIST 1.1 - Prior radiotherapy for melanoma - Prior systemic cancer therapies, including, but not limited to anti-CTLA-4, anti-PD-1, anti-PD-L1 - No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years. - Patients will be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection - Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) - Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events. History or evidence of active autoimmune disease that requires high dose systemic treatment (ie, with use of disease modifying agents, corticosteroids or immuno-suppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Evidence of clinically significant immunosuppression such as the following: - Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease. - Concurrent opportunistic infection. - Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. - Active herpetic skin lesions or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis). - Requirement of intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use. - Previous treatment with talimogene laherparepvec or any other oncolytic virus. - Received live vaccine within 28 days prior to enrollment. - Subject has known sensitivity to talimogene laherparepvec or any of its components to be administered during dosing. - Female subject of childbearing potential who is unwilling to use highly effective method(s) of effective contraception during study treatment and through 5 months after the last dose of study medication (per protocol through 3 months after the last dose of talimogene laherparepvec and through 5 months after the last dose of nivolumab). - Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec. - Subjects who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or infants under the age of 3 months, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec. - No Allergies and Adverse Drug Reaction? - History of allergy to study drug components? - History of severe hypersensitivity reaction to any monoclonal antibody - No underlying medical conditions that, in the Investigator's opinion, will make the ad-ministration of study drug hazardous or obscure the interpretation of to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate if neo-adjuvant combination of talimogene laherparepvec and nivolumab will achieve a pathologic response rate of 45% complete responses (either ‘pathological complete response (pCR)’ or ‘pathological near complete response (near-pCR)’, in patients with stage IIIB/C/D/IV M1a (AJCC 8) melanoma;Secondary Objective: - To investigate the rate of delays or failures (delays =14 days) to perform surgery - To investigate the effect of neo-adjuvant comabination of talimogene laherparepvec and nivolumab on relapse free survival (RFS) - To determine the safety of neo-adjuvant combination of talimogene laherparepvec and nivolumab - To acquire tumor tissue for prognostic and predictive biomarker research. ;Primary end point(s): Pathologic response according to central revision by pathology of NKI (complete response, near complete response (<10% vital tumor remaining));Timepoint(s) of evaluation of this end point: 9 weeks after start of the neo-adjuvant treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of delay of surgery >14 days and rate of failure to perform surgery de-fined as no surgery at all (due to PD or AE) - Relapse free survival (RFS) as defined from date of surgery until date of first replase (regardless of site) - Safety of neo-adjuvant combination of talimogene laherparepvec and nivolumab according to CTCAE v5.0 - Description of possible prognostic and predictive biomarkers ;Timepoint(s) of evaluation of this end point: 9 weeks after start of neo-adjuvant treatment During follow-up | — |
Countries
Netherlands
Contacts
Public ContactStudy coordinator John Haanen
Antoni van Leeuwenhoek Ziekenhuis
Outcome results
None listed