Ignite Creation Date:
2024-05-06 @ 3:03 PM
Last Modification Date:
2024-10-26 @ 1:42 PM
Study NCT ID:
NCT04508140
Status:
TERMINATED
Last Update Posted:
2022-12-13
First Post:
2020-08-05
Brief Title:
Study of BO-112 With Pembrolizumab for Colorectal or GastricGEJ Cancer With Liver Metastasis
Sponsor:
Highlight Therapeutics
Organization:
Highlight Therapeutics
Study Overview
Official Title:
Phase IIa Open-label Clinical Study of Intratumoural Administration of BO-112 in Combination With Pembrolizumab in Subjects With Liver Metastasis From Colorectal Cancer or GastricGastro-oesophageal Junction Cancer
Status:
TERMINATED
Status Verified Date:
2022-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Low recruitment rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open single arm multicenter phase 2 trial in which BO-112 will be administered intratumorally in combination with intravenous pembrolizumab in patients with liver metastasis from colorectal gastric or gastroesophageal junction cancers The objective is to reverse the primary resistance that a subgroup of patients from these tumors having microsatellite stability present to the PD-1 inhibitors Treatment will be administered every 3 weeks with the exception of the first cycle in which BO-112 will be also administered on D8 for up to 2 years
The primary objective is overall response rate based on RECIST 11 and safety specifically referred to treatment emergent adverse events TEAEs with severity Grade 3 related to the study treatment NCI-CTCAE v 50 The secondary endpoints include other efficacy endpoints duration of response disease control rate progression-free survival overall survival at 6 months all based on RECIST 11 and overall response rate based on a specific tumor assessment criteria to evaluate the response to immunotherapies IRECIST and safety in this case considering the number and proportion of subjects with treatment TEAEs any grade In addition the changes in the tumor microenvironment induced by the injection of BO-112 will be also evaluated as exploratory endpoints
The primary objective is overall response rate based on RECIST 11 and safety specifically referred to treatment emergent adverse events TEAEs with severity Grade 3 related to the study treatment NCI-CTCAE v 50 The secondary endpoints include other efficacy endpoints duration of response disease control rate progression-free survival overall survival at 6 months all based on RECIST 11 and overall response rate based on a specific tumor assessment criteria to evaluate the response to immunotherapies IRECIST and safety in this case considering the number and proportion of subjects with treatment TEAEs any grade In addition the changes in the tumor microenvironment induced by the injection of BO-112 will be also evaluated as exploratory endpoints
Detailed Description:
The purpose of this Phase II study is to evaluate the safety tolerability antitumoural activity and systemic exposure of repeated IT administrations of BO-112 percutaneously injected into a hepatic metastatic lesion in combination with pembrolizumab administered intravenously
This is an open-label non-comparative 2-cohort study with a Simons 2-stage design which will include up to 69 evaluable adult subjects with un resectable liver metastasis suitable for IT injection from CRC or GCGEJ who are naive to anti-PD1PDL1 therapy
Cohort A will consist of up to 26 subjects with metastatic CRC who have received at least 2 prior standard of care systemic anticancer therapies for advancedmetastatic disease Bevacizumab may have been previously administrated Prior Anti-EGFR drugs are mandatory if applicable depending on the RAS status
Cohort B will consist of up to 43 subjects with gastric or GCGEJ who have received at least 1 prior standard of care systemic anticancer therapy for advancedmetastatic disease Prior Her2 blockade will be mandatory in those patients with Her2 positive tumors
The aim of this study is to reverse the primary resistance that the subgroup of patients from these 2 cohorts who present microsatellite stability MSS in which data from previous clinical trials have demonstrate that the inhibition of PD-1 has no proven efficacy For that purpose the MSI status will be determined in the pre-treatment biopsy done on C1D1 before the first BO-112 administration Those patients with a MSI status will continue under study treatment but will be replaced and will not be considered for the efficacy assessment only for the safety assessment Those patients having a MSS status will be considered bot both assessments
The recommended dose for further clinical development of BO-112 is 1 mg administered in 17 mL volume based on the data from the 1122016-IT study the fist-in-human trial with BO-112 The planned dose of pembrolizumab for this study is 200 mg Study treatment will consist of BO-112 IT injections in combination with IV pembrolizumab infusions and will be administered in 3-week cycles For each cycle BO-112 IT injections will be administered after the pembrolizumab infusion either the same day or within a period of up to 36 hours after the pembrolizumab infusion for organisational feasibility at the site On the first cycle BO-112 will be administered on D1 and D8
The BO-112 IT injections will be administered by an interventional radiologist under ultrasound guidance or occasional CT scan guidance at the discretion of the interventional radiologist
Study treatment should continue as long as there is clinical benefit and it is tolerated up to a maximum of approx 2 years corresponding to 35 treatment cycles
This is an open-label non-comparative 2-cohort study with a Simons 2-stage design which will include up to 69 evaluable adult subjects with un resectable liver metastasis suitable for IT injection from CRC or GCGEJ who are naive to anti-PD1PDL1 therapy
Cohort A will consist of up to 26 subjects with metastatic CRC who have received at least 2 prior standard of care systemic anticancer therapies for advancedmetastatic disease Bevacizumab may have been previously administrated Prior Anti-EGFR drugs are mandatory if applicable depending on the RAS status
Cohort B will consist of up to 43 subjects with gastric or GCGEJ who have received at least 1 prior standard of care systemic anticancer therapy for advancedmetastatic disease Prior Her2 blockade will be mandatory in those patients with Her2 positive tumors
The aim of this study is to reverse the primary resistance that the subgroup of patients from these 2 cohorts who present microsatellite stability MSS in which data from previous clinical trials have demonstrate that the inhibition of PD-1 has no proven efficacy For that purpose the MSI status will be determined in the pre-treatment biopsy done on C1D1 before the first BO-112 administration Those patients with a MSI status will continue under study treatment but will be replaced and will not be considered for the efficacy assessment only for the safety assessment Those patients having a MSS status will be considered bot both assessments
The recommended dose for further clinical development of BO-112 is 1 mg administered in 17 mL volume based on the data from the 1122016-IT study the fist-in-human trial with BO-112 The planned dose of pembrolizumab for this study is 200 mg Study treatment will consist of BO-112 IT injections in combination with IV pembrolizumab infusions and will be administered in 3-week cycles For each cycle BO-112 IT injections will be administered after the pembrolizumab infusion either the same day or within a period of up to 36 hours after the pembrolizumab infusion for organisational feasibility at the site On the first cycle BO-112 will be administered on D1 and D8
The BO-112 IT injections will be administered by an interventional radiologist under ultrasound guidance or occasional CT scan guidance at the discretion of the interventional radiologist
Study treatment should continue as long as there is clinical benefit and it is tolerated up to a maximum of approx 2 years corresponding to 35 treatment cycles
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2019-004624-38 | EUDRACT_NUMBER | None | None |
| KEYNOTE-A06 | OTHER | Merck | None |