Ignite Creation Date:
2024-05-06 @ 8:11 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06284590
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-08
First Post:
2024-01-26
Brief Title:
Study of the Efficacy of Intratumoral L19IL2 or L19TNF or L19IL2L19TNF in Combination With Pembrolizumab in Unresectable Melanoma Patients
Sponsor:
Philogen SpA
Organization:
Philogen SpA
Study Overview
Official Title:
A Phase 2 Three-arm Randomized Study of the Efficacy of Intratumorally Administered L19IL2 or L19TNF or L19IL2L19TNF All in Combination With Systemic Anti-PD1 Pembrolizumab in Stage III and IV Unresectable Melanoma Patients With Resistance to or Progressing Upon Anti-PD1 Checkpoint Inhibitors and With Presence of Injectable Metastases
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INTACTMeRCI
Brief Summary:
The trial aims to evaluate the efficacy of single agent L19IL2 single agent L19TNF and combination L19IL2L19TNF 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
Detailed Description:
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 L19IL2L19TNF in combination with systemic anti-PD1 pembrolizumab immunotherapy will be used
In the study 162 patients will be randomized in a 111 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 L19IL2L19TNF Arm 3
This is an open-label study so there is no blinding
The study consists of a two-week screening period followed by a 4-weeks open-label intralesional treatment period with immunocytokines ICKs either L19IL2 L19TNF or L19IL2L19TNF Pembrolizumab will be administered by iv infusion 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
Follow-up for progression free survival will be performed up to 2 years after first intralesional treatment Survival information will be collected up to 3 years after first intralesional treatment
A safety run-in will be performed on the first 12 patients enrolled in each arm of the study Patients will be evaluated during the first 21-days cycle for the occurrence of the treatment-related adverse events All toxicities will be graded using NCI CTCAE Version 50 based on the investigator assessment to be possibly probably or definitely related to study treatment administration
In addition to this safety information collected will be routinely reviewed by the Data and Safety Monitoring Board DSMB in order to identify possible safety concerns
The primary objective of the study is to demonstrate the efficacy of intralesional treatment with ICKs in combination with systemic anti-PD1 immunotherapy with pembrolizumab to induce objective responses in advanced melanoma patients with resistance to or progressing upon anti-PD1 checkpoint inhibitors
Primary endpoint of the study is the Confirmed Objective Response Rate ORR CR PR in all three arms over a period of up to 2 years after first intralesional treatment according to RECIST v11 criteria in each arm of the study The primary analysis will be performed in the Intention-to-Treat population ITT
For each of the three treatment arms secondary objectives include efficacy and safety of intralesional treatment with ICKs
The secondary endpoints include
Best overall response BOR the best overall response is the best response recorded from the start of the treatment until disease progressionrecurrence according to RECIST v11 criteria
Duration of response DoR
Pathological response of one target lesion injected with ICKs at 18 weeks after first treatment
Confirmed ORR over a period of up to 2 years after first intralesional treatment according to iRECIST see Appendix 1 and itRECIST 1 criteria in each arm of the study
Progression-free survival PFS from time of randomization
Overall survival OS from randomization
Number frequency and grading of adverse events AEs and serious adverse events SAEs related to intralesional therapy with ICKs in combination with systemic anti-PD1 therapy
End of treatment last day of anti-PD1 therapy or until progression or unacceptable toxicity
End of study corresponds to the last patient last visit LPLV
In the study 162 patients will be randomized in a 111 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 L19IL2L19TNF Arm 3
This is an open-label study so there is no blinding
The study consists of a two-week screening period followed by a 4-weeks open-label intralesional treatment period with immunocytokines ICKs either L19IL2 L19TNF or L19IL2L19TNF Pembrolizumab will be administered by iv infusion 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
Follow-up for progression free survival will be performed up to 2 years after first intralesional treatment Survival information will be collected up to 3 years after first intralesional treatment
A safety run-in will be performed on the first 12 patients enrolled in each arm of the study Patients will be evaluated during the first 21-days cycle for the occurrence of the treatment-related adverse events All toxicities will be graded using NCI CTCAE Version 50 based on the investigator assessment to be possibly probably or definitely related to study treatment administration
In addition to this safety information collected will be routinely reviewed by the Data and Safety Monitoring Board DSMB in order to identify possible safety concerns
The primary objective of the study is to demonstrate the efficacy of intralesional treatment with ICKs in combination with systemic anti-PD1 immunotherapy with pembrolizumab to induce objective responses in advanced melanoma patients with resistance to or progressing upon anti-PD1 checkpoint inhibitors
Primary endpoint of the study is the Confirmed Objective Response Rate ORR CR PR in all three arms over a period of up to 2 years after first intralesional treatment according to RECIST v11 criteria in each arm of the study The primary analysis will be performed in the Intention-to-Treat population ITT
For each of the three treatment arms secondary objectives include efficacy and safety of intralesional treatment with ICKs
The secondary endpoints include
Best overall response BOR the best overall response is the best response recorded from the start of the treatment until disease progressionrecurrence according to RECIST v11 criteria
Duration of response DoR
Pathological response of one target lesion injected with ICKs at 18 weeks after first treatment
Confirmed ORR over a period of up to 2 years after first intralesional treatment according to iRECIST see Appendix 1 and itRECIST 1 criteria in each arm of the study
Progression-free survival PFS from time of randomization
Overall survival OS from randomization
Number frequency and grading of adverse events AEs and serious adverse events SAEs related to intralesional therapy with ICKs in combination with systemic anti-PD1 therapy
End of treatment last day of anti-PD1 therapy or until progression or unacceptable toxicity
End of study corresponds to the last patient last visit LPLV
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MK-3475-F20 | OTHER | None | None |
| KEYNOTE-F20 | OTHER | missing | None |