Ignite Creation Date:
2024-05-06 @ 6:25 PM
Last Modification Date:
2024-10-26 @ 2:47 PM
Study NCT ID:
NCT05650918
Status:
COMPLETED
Last Update Posted:
2023-10-12
First Post:
2022-08-08
Brief Title:
MesoPherMitazalimab-combination Therapy in Metastatic Pancreatic Disease REACtiVe-2 Trial
Sponsor:
Joachim Aerts MD PhD
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Dendritic Cells Loaded With Allogeneic Tumor Lysate MesoPher in Combination With a CD40 Agonist Mitazalimab in Metastatic Pancreatic Disease
Status:
COMPLETED
Status Verified Date:
2023-10
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:
REACtiVe-2
Brief Summary:
Pancreatic cancer is expected to be the second leading cause of cancer-related death in 2020 Pancreatic cancer is known as an immunological cold tumor It is thought that the characteristic desmoplastic stroma of established pancreatic adenocarcinomas acts as a physical as well as an immunosuppressive barrier leading to exclusion of T cells The use of CD40 agonists such as mitazalimab also known as JNJ-64457107 and ADC-1013 may convert pancreatic adenocarcinomas into immunological hot tumors by T-cell-dependent and T-cell-independent mechanisms Targeting the desmoplastic stroma thereby making the tumor more permeable for T-cell infiltration is seen as one of the assisting mechanisms Furthermore the immunological coldness of pancreatic cancers infers that tumor-reactive T-cell responses are absent or weak at best Dendritic cell therapy introduces tumor-specific T cells and in combination with a CD40 agonist may lead to synergistic anti-tumor responses which could be beneficial for pancreatic cancer patients
Detailed Description:
Rationale Pancreatic cancer is expected to be the second leading cause of cancer-related death in 2020 Pancreatic cancer is known as an immunological cold tumor It is thought that the characteristic desmoplastic stroma of established pancreatic adenocarcinomas acts as a physical as well as an immunosuppressive barrier leading to exclusion of T cells The use of CD40 agonists such as mitazalimab also known as JNJ-64457107 and ADC-1013 may convert pancreatic adenocarcinomas into immunological hot tumors by T-cell-dependent and T-cell-independent mechanisms Targeting the desmoplastic stroma thereby making the tumor more permeable for T-cell infiltration is seen as one of the assisting mechanisms Furthermore the immunological coldness of pancreatic cancers infers that tumor-reactive T-cell responses are absent or weak at best Dendritic cell therapy introduces tumor-specific T cells and in combination with a CD40 agonist may lead to synergistic anti-tumor responses which could be beneficial for pancreatic cancer patients
Objective To investigate safety and tolerability as well as the induced immune response upon MesoPhermitazalimab combination therapy in metastasized pancreatic cancer after standard-of-care SOC treatment with modified FOLFIRINOX
Study design Open-label single-center phase I dose finding study using a modified toxicity probability interval mTPI design
Study population Adults with metastatic pancreatic cancer after SOC treatment with modified FOLFIRINOX
Intervention Leukapheresis is performed after which monocytes are used for differentiation to dendritic cells Autologous dendritic cells pulsed with an allogeneic tumor lysate MesoPher will be administered intra-dermally and intravenously 3 times every 2 weeks Booster vaccinations are given after 3 and 6 months On the same day after administration of MesoPher a CD40 agonist mitazalimab will be administered intravenously
Study parametersendpoints The main study endpoint are the dose-limiting toxicities of MesoPhermitazalimab combination therapy The secondary endpoints are the induced immune responses on therapy and the radiographical response rate according to RECIST and iRECIST
Nature and extent of the burden and risks associated with participation benefit and group relatedness Patients have to undergo additional outpatient clinic visits for this study and additional invasive procedures specifically for this trial eg intravenous catheter placement and tumor metastasis biopsies Although these are invasive procedures associated risks are limited Intravenous access is necessary during every visit ie for leukapheresis for drawing blood samples and for the administration of study medication Leukapheresis is a standard procedure and will be performed according to our institutional guidelines Leukapheresis demonstrates a limited risk for transient thrombocytopenia and leukopenia Previous clinical studies have shown that injection with tumor lysate-pulsed dendritic cells MesoPher was well tolerated without major systemic toxicity with the exception of low-grade flu-like symptoms REACtiVE Trial NL6716900018 DENIMMM04 NCT03610360 MM03 NL4433000014 NCT02395679
Also intravenous injection of mitazalimab up to 1200 µgkg was well tolerated with manageable side effects There are currently no trials investigating this combination therapy Combining two immunomodulatory drugs increases the risk for toxicity The objective of this phase I study is to investigate safety and tolerability of administrating MesoPhermitazalimab combination therapy in metastatic pancreatic cancer patients Patients may have potential beneficial anti-tumor responses following study medication
Objective To investigate safety and tolerability as well as the induced immune response upon MesoPhermitazalimab combination therapy in metastasized pancreatic cancer after standard-of-care SOC treatment with modified FOLFIRINOX
Study design Open-label single-center phase I dose finding study using a modified toxicity probability interval mTPI design
Study population Adults with metastatic pancreatic cancer after SOC treatment with modified FOLFIRINOX
Intervention Leukapheresis is performed after which monocytes are used for differentiation to dendritic cells Autologous dendritic cells pulsed with an allogeneic tumor lysate MesoPher will be administered intra-dermally and intravenously 3 times every 2 weeks Booster vaccinations are given after 3 and 6 months On the same day after administration of MesoPher a CD40 agonist mitazalimab will be administered intravenously
Study parametersendpoints The main study endpoint are the dose-limiting toxicities of MesoPhermitazalimab combination therapy The secondary endpoints are the induced immune responses on therapy and the radiographical response rate according to RECIST and iRECIST
Nature and extent of the burden and risks associated with participation benefit and group relatedness Patients have to undergo additional outpatient clinic visits for this study and additional invasive procedures specifically for this trial eg intravenous catheter placement and tumor metastasis biopsies Although these are invasive procedures associated risks are limited Intravenous access is necessary during every visit ie for leukapheresis for drawing blood samples and for the administration of study medication Leukapheresis is a standard procedure and will be performed according to our institutional guidelines Leukapheresis demonstrates a limited risk for transient thrombocytopenia and leukopenia Previous clinical studies have shown that injection with tumor lysate-pulsed dendritic cells MesoPher was well tolerated without major systemic toxicity with the exception of low-grade flu-like symptoms REACtiVE Trial NL6716900018 DENIMMM04 NCT03610360 MM03 NL4433000014 NCT02395679
Also intravenous injection of mitazalimab up to 1200 µgkg was well tolerated with manageable side effects There are currently no trials investigating this combination therapy Combining two immunomodulatory drugs increases the risk for toxicity The objective of this phase I study is to investigate safety and tolerability of administrating MesoPhermitazalimab combination therapy in metastatic pancreatic cancer patients Patients may have potential beneficial anti-tumor responses following study medication
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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