Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06630611
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-26
Brief Title:
Evaluation of a Pragmatic Approach to Adoptive Cell Therapy ACT Using an IL2 Analog ANV419 vs High Dose IL2 After Tumor Infiltrating Lymphocytes TIL Therapy in Patients With Melanoma NSCLC and Cervical Cancer PragmaTIL
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Phase II Randomized Study Evaluating a Pragmatic Approach to Adoptive Cell Therapy ACT Using an IL2 Analog ANV419 vs High Dose IL2 After Tumor Infiltrating Lymphocytes TIL Therapy in Patients With Melanoma NSCLC and Cervical Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PragmaTIL
Brief Summary:
Background
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity
TIL-based ACT Adoptive cell therapy using tumor-infiltrating lymphocytes product is a modality of ACT used to treat patients with multiple types of cancer and it consists in the adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes obtained from tumor resection or tumor biopsies in patients following a non-myeloablative lymphodepleting NMA-LD chemotherapy Ex vivo expansion of TIL relies on the non-specific expansion of lymphocytes present in tumor single cell suspensions or tumor fragments in high dose IL-2
Although proven efficacy in selected the HD-IL-2 use remains relatively restricted due to toxicity Due to the short serum half-life and the need to achieve an immune-modulatory effect in the tissues IL-2 must be given in doses that induce severe systemic toxicities including capillary leak syndrome CLS pulmonary edema hypotension acute renal insufficiency and rarely myocarditis limiting its applicability in cancer Studies comparing HD-IL-2 with lower doses both in renal cell carcinoma and metastatic melanoma to minimize toxicity demonstrated the superiority of the high dose regimens in both diseases These drawbacks of HD-IL-2 use encouraged the development of improved IL-2-based biologic agents with higher selectivity for effector immune cell subsets reduced toxicity and prolonged half-life
ANV419 is a novel IL-2 agent which has been developed as a preferentially IL-2Rβγ directed fusion protein with a longer half-life It has shown high effector selectivity and a favorable safety profile in preclinical testing including in nonhuman primates and it has been investigated in an ongoing open-label dose-escalation Phase I Study in multiple tumor types he safety profile of ANV419 is characterized by pyrexia nausea vomiting ALTAST changes and CRS in some patients Most events are low grade and self-limiting and manageable with standard supportive care ANV419 was well-tolerated by most patients No patient discontinued treatment due to treatment related AE
Taking all the previous information into account the primary objectives of this study are
1 To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade 3 relevant adverse events related to interleukin use based on Common Terminology Criteria for Adverse Events v50 - CTCAE v50 compared to TIL-ACT using HD-IL-2
2 To determine whether TIL-ACT using the IL-2 analog improves patients reported outcomes PRO compared to TIL-ACT using HD-IL-2
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity
TIL-based ACT Adoptive cell therapy using tumor-infiltrating lymphocytes product is a modality of ACT used to treat patients with multiple types of cancer and it consists in the adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes obtained from tumor resection or tumor biopsies in patients following a non-myeloablative lymphodepleting NMA-LD chemotherapy Ex vivo expansion of TIL relies on the non-specific expansion of lymphocytes present in tumor single cell suspensions or tumor fragments in high dose IL-2
Although proven efficacy in selected the HD-IL-2 use remains relatively restricted due to toxicity Due to the short serum half-life and the need to achieve an immune-modulatory effect in the tissues IL-2 must be given in doses that induce severe systemic toxicities including capillary leak syndrome CLS pulmonary edema hypotension acute renal insufficiency and rarely myocarditis limiting its applicability in cancer Studies comparing HD-IL-2 with lower doses both in renal cell carcinoma and metastatic melanoma to minimize toxicity demonstrated the superiority of the high dose regimens in both diseases These drawbacks of HD-IL-2 use encouraged the development of improved IL-2-based biologic agents with higher selectivity for effector immune cell subsets reduced toxicity and prolonged half-life
ANV419 is a novel IL-2 agent which has been developed as a preferentially IL-2Rβγ directed fusion protein with a longer half-life It has shown high effector selectivity and a favorable safety profile in preclinical testing including in nonhuman primates and it has been investigated in an ongoing open-label dose-escalation Phase I Study in multiple tumor types he safety profile of ANV419 is characterized by pyrexia nausea vomiting ALTAST changes and CRS in some patients Most events are low grade and self-limiting and manageable with standard supportive care ANV419 was well-tolerated by most patients No patient discontinued treatment due to treatment related AE
Taking all the previous information into account the primary objectives of this study are
1 To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade 3 relevant adverse events related to interleukin use based on Common Terminology Criteria for Adverse Events v50 - CTCAE v50 compared to TIL-ACT using HD-IL-2
2 To determine whether TIL-ACT using the IL-2 analog improves patients reported outcomes PRO compared to TIL-ACT using HD-IL-2
Detailed Description:
This is a an open-label randomized pragmatic multicenter phase II clinical trial to compare the safety quality of life and efficacy of current protocols of adoptive cell therapy based on tumorinfiltrating lymphocytes TIL-ACT established at each institution facility through the randomization between two types of following interleukin used for engrafting and in vivo expansion of TILs standard high-dose HD IL-2600000 IUkg or ANV419
Total number of patients included in the trial will be 40 Of the total 40 patients the first 10 patients recruited in the study will be metastatic melanoma patients The melanoma and non-melanoma cohorts will be equally distributed between the two arms Patients will be randomized to start treatment with either HD-IL-2 Control arm or with ANV419 Experimental arm
The objectives of this study are the following
Primary objectives
To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade 3 relevant adverse events related to interleukin use based on Common Terminology Criteria for Adverse Events v50 - CTCAE v50 compared to TIL-ACT using HD-IL-2
To determine whether TIL-ACT using the IL-2 analog improves patients reported outcomes PRO compared to TIL-ACT using HD-IL-2
Secondary objectives
To evaluate the safety and the tolerability of TIL-ACT using the IL-2 analog ANV419 compared to TIL-ACT using HD-IL-2
To evaluate short-term efficacy outcomes in patients receiving the IL-2 analog ANV419 or HD-IL-2
To evaluate long-term efficacy outcomes in patients receiving the IL-2 analog ANV419 or HD-IL-2
To evaluate the quality of life QoL and symptomatology in patients receiving the IL-2 analog ANV419 or HD-IL-2
To evaluate anxiety and depression in patients receiving the IL-2 analog ANV419 or HD-IL-2
To develop the health technology assessment HTA of TIL-ACT using ANV419 via the analysis of cost-effectiveness budget impact reimbursement strategies user acceptance and technical feasibility This assessment together with a social return of investment SROI analysis will provide relevant information to participant member states regarding the possibility of implementing optimized and affordable treatments in their healthcare systems
Exploratory objectives
To evaluate the impact of the different cytokine regimens on CD8 NK and Treg proliferation cytokine secretion profile as well as the persistence and transcriptomicphenotypic profile of the infused TIL product at different times following TIL infusion
To correlate the presence and persistence of tumor- and neoantigen- reactive TIL and their transcriptomicphenotypic profile with clinical outcome
To evaluate the influence of tumor and neoantigen heterogeneity measured through tumor and cell free DNA sequencing prior to and during treatment
To evaluate biometric physiological parameters mobility heart rate SpO2 and sleep cycle through wearable devices during and after treatmen
Total number of patients included in the trial will be 40 Of the total 40 patients the first 10 patients recruited in the study will be metastatic melanoma patients The melanoma and non-melanoma cohorts will be equally distributed between the two arms Patients will be randomized to start treatment with either HD-IL-2 Control arm or with ANV419 Experimental arm
The objectives of this study are the following
Primary objectives
To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade 3 relevant adverse events related to interleukin use based on Common Terminology Criteria for Adverse Events v50 - CTCAE v50 compared to TIL-ACT using HD-IL-2
To determine whether TIL-ACT using the IL-2 analog improves patients reported outcomes PRO compared to TIL-ACT using HD-IL-2
Secondary objectives
To evaluate the safety and the tolerability of TIL-ACT using the IL-2 analog ANV419 compared to TIL-ACT using HD-IL-2
To evaluate short-term efficacy outcomes in patients receiving the IL-2 analog ANV419 or HD-IL-2
To evaluate long-term efficacy outcomes in patients receiving the IL-2 analog ANV419 or HD-IL-2
To evaluate the quality of life QoL and symptomatology in patients receiving the IL-2 analog ANV419 or HD-IL-2
To evaluate anxiety and depression in patients receiving the IL-2 analog ANV419 or HD-IL-2
To develop the health technology assessment HTA of TIL-ACT using ANV419 via the analysis of cost-effectiveness budget impact reimbursement strategies user acceptance and technical feasibility This assessment together with a social return of investment SROI analysis will provide relevant information to participant member states regarding the possibility of implementing optimized and affordable treatments in their healthcare systems
Exploratory objectives
To evaluate the impact of the different cytokine regimens on CD8 NK and Treg proliferation cytokine secretion profile as well as the persistence and transcriptomicphenotypic profile of the infused TIL product at different times following TIL infusion
To correlate the presence and persistence of tumor- and neoantigen- reactive TIL and their transcriptomicphenotypic profile with clinical outcome
To evaluate the influence of tumor and neoantigen heterogeneity measured through tumor and cell free DNA sequencing prior to and during treatment
To evaluate biometric physiological parameters mobility heart rate SpO2 and sleep cycle through wearable devices during and after treatmen
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None