A Phase 2 interventional study of Hepatic Biopsy and BO-112 with pembrolizumab in Colorectal Cancer, Gastric Cancer and Oesophageal Cancer, sponsored by Highlight Therapeutics. Terminated at 12 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-29.
Sponsored by Highlight Therapeutics · Phase 2, Interventional, and Treatment
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 1.1 and safety, specifically referred to treatment emergent adverse events (TEAEs) with severity ≥ Grade 3 related to the study treatment (NCI-CTCAE v 5.0). 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 1.1, 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 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 Simon's 2-stage design which will include up to 69 evaluable adult subjects with un resectable liver metastasis suitable for IT injection from CRC or GC/GEJ who are naive to anti-PD1/PDL1 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 advanced/metastatic 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 GC/GEJ who have received at least 1 prior standard of care systemic anticancer therapy for advanced/metastatic 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 1.7 mL volume, based on the data from the 112/2016-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).
5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,458 are open to participants now.
This study's enrollment of 18 is below the median of 77 across 4,122 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Highlight Therapeutics is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Progression during or after, or have not tolerated therapy for advanced/metastatic disease as follows:
EXCLUSION CRITERIA
Cohort A consisted of 11 patients with CRC (microsatellite stable \[MSS\]) with nonresectable liver metastases suitable for IT injection and who had received at least 2 prior standard of care systemic anticancer therapies for advanced/metastatic disease. Patients who had resection of hepatic metastases and had hepatic recurrence, needed to have 1 or more prior standard of care systemic anticancer therapies in order to be eligible for this study. BO-112 was administered in the liver metastasis at the dose of 1mg (1.2 mL) in combination with intravenous pembrolizumab given at the fixed dose of 200 mg, every 3 weeks for up to 35 cycles (2 years). During the first cycle, BO-112 was administered on D1 and D8.
Procedure: Hepatic Biopsy · Drug: BO-112 with pembrolizumab
Cohort B consisted of 7 patients with gastric or GC/GEJ with nonresectable liver metastases suitable for IT injection and who had received at least 1 prior standard of care systemic anticancer therapy for advanced/metastatic disease. BO-112 was administered in the liver metastasis at the dose of 1 mg (1.2 mL) in combination with intravenous pembrolizumab given at the fixed dose of 200 mg, every 3 weeks for up to 35 cycles (2 years). During the first cycle, BO-112 was administered on D1 and D8.
Procedure: Hepatic Biopsy · Drug: BO-112 with pembrolizumab
In this trial a biopsy from the hepatic lesion to be injected will be mandatory on C1D1 and C2D1, prior to the BO-112 administration. On the same timepoints, a biopsy from a non-hepatic, non-injected lesion will be optional.
BO-112 was administered in the liver metastasis at the dose of 1mg (1.2 mL) in combination with intravenous pembrolizumab given at the fixed dose of 200 mg, every 3 weeks for up to 35 cycles (2 years). During the first cycle, BO-112 was administered on D1 and D8.
Also known as: KEYTRUDA®
Anti-tumour Efficacy:Overall Response Rate (ORR) Based on RECIST 1.1
ORR based on the best objective response (BOR) using RECIST 1.1 of repeated IT administrations of BO-112 in metastatic liver lesions in combination with IV pembrolizumab
Time frame: from baseline to approximately 8 months
Safety: Adverse Events
Number and proportion of subjects with study treatment-related TEAEs with severity Grade 3 and higher (NCI-CTCAE v 5.0)
Time frame: from baseline to approximately 8 months
Disease Control Rate Based on RECIST 1.1
Best response for CR, PR as well as stable disease (SD) using RECIST 1.1
Time frame: from baseline to approximately 8 months
Objective Response Rate Based iRECIST
Based on best overall response using RECIST modified for immune-based therapies (iRECIST)
Time frame: from baseline to approximately 8 months
Disease Control Rate Based on iRECIST
Comprising best response for CR, PR as well as SD using iRECIST
Time frame: from baseline to approximately 8 months
Progression-free Survival
Progression-free survival (PFS)
Time frame: from baseline to approximately 8 months
Overall Survival Rate
Number of subjects alive at 6 months
Time frame: at 6 months from enrolment
| Milestone | Cohort A | Cohort B |
|---|---|---|
| Started | 11 | 7 |
| Completed | 0 | 0 |
| Not completed | 11 | 7 |
| Withdrew: Adverse event | 2 | 2 |
| Withdrew: Withdrawal by subject | 0 | 2 |
| Withdrew: Progressive disease | 9 | 3 |
ORR based on the best objective response (BOR) using RECIST 1.1 of repeated IT administrations of BO-112 in metastatic liver lesions in combination with IV pembrolizumab
| Participants | Cohort A | Cohort B |
|---|---|---|
| Anti-tumour Efficacy:Overall Response Rate (ORR) Based on RECIST 1.1 | 0 | 0 |
Number and proportion of subjects with study treatment-related TEAEs with severity Grade 3 and higher (NCI-CTCAE v 5.0)
| Participants | Cohort A | Cohort B |
|---|---|---|
| Safety: Adverse Events | 4 | 4 |
Best response for CR, PR as well as stable disease (SD) using RECIST 1.1
| Participants | Cohort A | Cohort B |
|---|---|---|
| Disease Control Rate Based on RECIST 1.1 | 0 | 0 |
Based on best overall response using RECIST modified for immune-based therapies (iRECIST)
| Participants | Cohort A | Cohort B |
|---|---|---|
| Objective Response Rate Based iRECIST | 0 | 0 |
Comprising best response for CR, PR as well as SD using iRECIST
| Participants | Cohort A | Cohort B |
|---|---|---|
| Disease Control Rate Based on iRECIST | 0 | 0 |
Progression-free survival (PFS)
| months | Cohort A | Cohort B |
|---|---|---|
| Progression-free Survival | 1.35 (1.02 to 1.41) | 1.38 (0.95 to 2.56) |
Number of subjects alive at 6 months
| Participants | Cohort A | Cohort B |
|---|---|---|
| Overall Survival Rate | 9 | 3 |
Collected over from baseline to approximately 8 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort A | 2/11 (18.2%) | 5/11 (45.5%) | 11/11 (100%) |
| Cohort B | 2/7 (28.6%) | 2/7 (28.6%) | 7/7 (100%) |
| Event | Cohort A | Cohort B |
|---|---|---|
| pyrexiaGastrointestinal disorders | 3/11 | 0/7 |
| back painMusculoskeletal and connective tissue disorders | 2/11 | 0/7 |
| bacteriemiaInfections and infestations | 0/11 | 1/7 |
| syncopeNervous system disorders | 0/11 | 1/7 |
| alpha hemolytic streptococcal infectionInfections and infestations | 1/11 | 0/7 |
| COVID 19 pneumoniaInfections and infestations | 1/11 | 0/7 |
| Event | Cohort A | Cohort B |
|---|---|---|
| pyrexiaGeneral disorders | 8/11 | 4/7 |
| ChillsGeneral disorders | 5/11 | 0/7 |
| Abdominal painGastrointestinal disorders | 4/11 | 1/7 |
| NauseaGastrointestinal disorders | 4/11 | 1/7 |
| AstheniaGeneral disorders | 3/11 | 2/7 |
| Injection site painGeneral disorders | 0/11 | 2/7 |
| Aspartate aminotransferase increasedInvestigations | 2/11 | 2/7 |
| DiarrheaGastrointestinal disorders | 1/11 | 2/7 |
| VomitingGastrointestinal disorders | 2/11 | 2/7 |
| HyperthyroidismEndocrine disorders | 0/11 | 2/7 |
| Age, Categorical(Participants) | Cohort A | Cohort B | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 7 | 4 | 11 |
| >=65 years | 4 | 3 | 7 |
| Age, Continuous(years) | Cohort A | Cohort B | Total |
|---|---|---|---|
| Mean | 55.6 (37 to 74) | 56.1 (37 to 71) | 55.8 (37 to 74) |
| Sex: Female, Male(Participants) | Cohort A | Cohort B | Total |
|---|---|---|---|
| Female | 4 | 1 | 5 |
| Male | 7 | 6 | 13 |
| Race (NIH/OMB)(Participants) | Cohort A | Cohort B | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 11 | 7 | 18 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Cohort A | Cohort B | Total |
|---|---|---|---|
| Belgium | 1 | 1 | 2 |
| Italy | 1 | 0 | 1 |
| Spain | 9 | 6 | 15 |
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