Philogen S.p.A.
The trial aims to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and combination L19IL2+L19TNF given concurrently with anti-PD1 therapy compared to historical control of anti-PD-1 re-challenge alone for anti-PD1 refractory unresectable stage III-IV melanoma.
The present study is a randomized, open-label, three-arm, parallel phase 2 study. A Simon two-stage design for the study of the efficacy of intralesional therapy with L19IL2 or L19TNF or L19IL2/L19TNF in combination with systemic anti-PD1 pembrolizumab immunotherapy will be used. In the study, 162 patients will be randomized in a 1:1:1 ratio to receive: i) systemic pembrolizumab in combination with intralesional L19IL2 (Arm 1) or ii) systemic pembrolizumab in combination with intralesional L19TNF (Arm 2) or iii) systemic pembrolizumab in combination with intralesional L19IL2/L19TNF (Arm 3).…
Inclusion Criteria: 1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 2. Be \> or = 18 years of age on day of signing informed consent. 3. Participant with histologically or cytologically confirmed diagnosis of unresectable metastatic melanoma at stage III B, C, D or IV M1a (AJCC 8th ed.). Patients with Stage IVM1b, M1c and M1d oligometastatic disease \[up to 10 visceral lesions in aggregate including lung, liver, bone or brain, with or without lymph node involvement\], are eligible. However, patients with symptomatic…
Arm 1: The amount of L19IL2 that is intratumorally administered into injectable cutaneous, subcutaneous, and nodal tumors once weekly for up to 4 weeks is dependent on the size of the tumor. The maximum dose to be administered in a single treatment visit is 13 MioIU/1 mL of L19IL2.
Arm 2: The amount of L19TNF that is intratumorally administered into injectable cutaneous, subcutaneous, and nodal tumors once weekly for up to 4 weeks is dependent on the size of the tumor. The maximum dose to be administered in a single treatment visit is 400 μg/1 mL of L19TNF.
Arm 3: The amount of L19IL2/L19TNF that is intratumorally administered into injectable cutaneous, subcutaneous, and nodal tumors once weekly for up to 4 weeks is dependent on the size of the tumor. The maximum dose to be administered in a single treatment visit is 13MioIU L19IL2 + 400 μg L19TNF in a combined total volume of approximate 2 mL. In case that study drug-related, grade ≥ γ AEs are recorded after the first L19IL2/L19TNF dose administration, the L19TNF dose is reduced to 200 μg for the following administrations.
KEYTRUDA® will be administered by i.v. infusion as a dose of 200 mg on the first day of intralesional treatment with ICKs and will continue every 3 weeks for approximately 2 years, 35 cycles, 2 year cap or until disease progression or unacceptable toxicity, whichever comes first. ICKs intralesional treatment will be administered 30-60 minutes post administration of KEYTRUDA®.