1. Recurrence Free Survival (RFS) (Time Frame - From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.): RFS in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery and adjuvant therapy (Arm 2). RFS is defined as the difference between date of randomization (which represents Day 0 for both arms) and the date of first recurrence (local, regional, distant or new primary melanoma, whichever comes first) or death.
Secondary outcome:
1. Overall survival (OS) (Time Frame - From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first, assessed up to 72 months.): OS in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery and adjuvant therapy (Arm 2). OS is defined as the difference between date of randomization (which represents Day 0 for both arms) and the date of death.
2. Recurrence free survival (RFS) as determined by the local investigator (Time Frame - From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.): RFS after randomization in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery and adjuvant therapy (Arm 2). RFS is defined as the difference between date of randomization (which represents Day 0 for both arms) and the date of first recurrence (local, regional, distant or new primary melanoma, whichever comes first) or death.
3. Pathological response (only for patients in Arm 1) (Time Frame - Time Frame: Assessed at the time of surgical resection of the tumor lesions): Categorization of pathological response as: p Complete Response, p near-Complete Response, p Partial Response, p None Response
4. Adverse Events (AE) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the first follow-up visit (up to approximately 5 months).): Percentage of Patients in Each Treatment Group with AEs, AEs with CTCAE grade ≥3
5. Serious Adverse Event (SAEs) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).): Percentage of Patients in Each Treatment Group with Drug-Related Adverse Events, Serious Adverse Event (SAEs)
6. Drug-Induced Liver Injury (DILI) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).): Number of patients with Drug-Induced Liver Injury (DILI)
7. Adverse Events of Special Interest (AESI) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).): Number of patients with Adverse Events of Special Interest (AESI)
8. Percentage of Subjects with Haematological/chemical Laboratory Abnormalities (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).)
9. Percentage of participants with Electrocardiogram (ECG) and echocardiogram (ECHO) abnormality findings. (Time Frame - 1) day 0-14 (screening) for both arm; 2) at week 5 (Safety assessment) only for arm 1.): Data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment.
10. Number of subjects with a clinically significant change from baseline in physical examination (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months))
11. Concomitant medication (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months)): Number of subject with concomitant medication
12. Human anti-fusion protein antibodies (HAFA) (Time Frame - 1) day 0-14 (screening) for arm 1; 2) at week 5 (Safety assessment) for Arm 1; 3) at week 12 (only first follow-up) for Arm 1.): Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF
13. Vital signs (blood pressure) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).): Number of subjects with a clinically significant change from baseline in vital signs (blood pressure) by visit
14. Number of subjects with a clinically significant change from baseline in vital signs (heart rate) by visit (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months))
15. Number of subjects with a clinically significant change from baseline in vital signs (body temperature) by visit (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months))
Experimental: Daromun plus Surgery and Adjuvant therapy (Arm 1) Two-weeks screening period and a 4-weeks open-label treatment period, followed by surgery within a maximum of another 4 weeks and adjuvant therapy (Arm 1).
Active Comparator: Surgery and adjuvant therapy (Arm 2) Patients in the control arm (Arm 2) will receive direct surgery within 4 weeks from randomization, followed by adjuvant therapy.
Daromun: Patients will receive intratumoral administrations into injectable cutaneous, subcutaneous, and nodal tumors of Daromun once weekly for up to 4 weeks. Surgery will follow within 4 weeks.
Surgery: Patients in Arm 2 will receive surgery within 4 weeks from randomisation.
Adjuvant therapy: Patients will receive adjuvant therapy at the investigator's discretion following the surgery.
Quelle: ClinicalTrials.gov
Sie können folgenden Inhalt einem Kollegen empfehlen:
"Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C Melanoma Patients"
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