- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04508140
Study of BO-112 With Pembrolizumab for Colorectal or Gastric/GEJ Cancer With Liver Metastasis
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 Gastric/Gastro-oesophageal Junction Cancer
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 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).
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Brussels, Belgium
- Institut Jules Bordet
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Brussels, Belgium
- UCL St-Luc
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Edegem, Belgium
- University Hospital Antwerp (UZA)
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Gent, Belgium
- Universitair Ziekenhus Gent
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Genova, Italy
- IRCCS Ospedale Policlinico San Martino
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Milan, Italy
- Azienda Ospedaliera Ospedale Niguarda Ca'Granda
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Barcelona, Spain
- Hospital Valle Hebrón
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Madrid, Spain
- Hospital Ramón y Cajal
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Madrid, Spain
- Hospital Gregorio Marañon
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Pamplona, Spain
- Clinica Universitaria de Navarra
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Valencia, Spain
- Hospital Clinico de Valencia
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Cordoba
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Córdoba, Cordoba, Spain
- Hospital Reina Sofia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Nonresectable liver metastasis(es) of colorectal or gastric/gastro-oesophageal junction cancer (GC/GEJ). History of resection for liver metastasis is allowed.
- Histological or cytological proof of colorectal (Cohort A) or GC/GEJ cancer (Cohort B).
Progression during or after, or have not tolerated therapy for advanced/metastatic disease as follows:
- Cohort A (CRC): at least 2 lines of fluoropyrimidine, irinotecan and/or oxaliplatin containing therapy with or without bevacizumab; if epidermal growth factor receptor (EGFR) positive/RAS wild type, prior anti-EGFR treatment is required. Incase of prior resection of hepatic metastasis with hepatic recurrence, only 1 prior line of fluoropyrimidine, irinotecan and/or oxaliplatin containing therapy is required.
- Cohort B (GC/GEJ): fluoropyrimidine and platinum containing treatment; if Human epidermal growth factor receptor 2 (HER-2) positive, also prior anti-HER-2 treatment is required.
- At least 1 liver metastasis of minimum 20 mm in diameter that is suitable for percutaneous, IT injection .
- Presence of at least 1 measurable lesion according to RECIST v1.1. Note: this may be the liver metastasis selected for injection if it is the only measurable lesion present.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate haematologic and end-organ function
EXCLUSION CRITERIA
- Prior treatment with an anti-PD1, anti-PDL1 or anti-PDL2 agent, an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137) or any Toll-like receptor (TLR) agonist.
- Liver metastasis(es) with macroscopic tumour infiltration into the main portal vein, hepatic vein or vena cava.
- Contraindications to tumour biopsy and injections of the hepatic metastasis(es).
- Chemotherapy, definitive (curative) radiation, or biological cancer therapy within 4 weeks prior to the first dose of study treatment.
- Palliative radiotherapy (≤ 2 weeks of radiotherapy) within 1 week of start of study treatment.
- Clinically active central nervous system (CNS) metastases and/or carcinomatosis meningitis.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Single Arm
The study treatment consists of the combination of BO-112 given intratumorally inside the liver metastasis at the dose of 1gm in 1.2 mL in combination with intravenous pembrolizumab given at the fixed dose of 200 mg.
This treatment will be given every 3 weeks, with a maximum duration of 35 cycles (2 years).
Of note, during the first cycle, BO-112 will be administered on D1 and D8.
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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.
. The study treatment consists of the combination of BO-112 given intratumorally inside the liver metastasis at the dose of 1gm in 1.2 mL in combination with intravenous pembrolizumab given at the fixed dose of 200 mg.
This treatment will be given every 3 weeks, with a maximum duration of 35 cycles (2 years).
Of note, during the first cycle, BO-112 will be administered on D1 and D8.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anti-tumour efficacy:overall response rate
Time Frame: Throughout study completion, an average of 3 years.
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ORR based on the BOR using RECIST 1.1 of repeated IT administrations of BO-112 in metastatic liver lesions in combination with IV pembrolizumab
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Throughout study completion, an average of 3 years.
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Safety: Adverse Events
Time Frame: Throughout study completion, an average of 3 years
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Number and proportion of subjects with study treatment-related TEAEs with severity Grade 3 (NCI-CTCAE v 5.0)
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Throughout study completion, an average of 3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease control rate
Time Frame: Throughout study completion, an average of 3 years
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Best response for CR, PR as well as stable disease (SD) using RECIST 1.1
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Throughout study completion, an average of 3 years
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Objective response rate
Time Frame: Throughout study completion, an average of 3 years
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Based on best overall response using RECIST modified for immune-based therapies (iRECIST)
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Throughout study completion, an average of 3 years
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Disease Control Rate
Time Frame: Throughout study completion, an average of 3 years
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Comprising best response for CR, PR as well as SD using iRECIST
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Throughout study completion, an average of 3 years
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Duration of response
Time Frame: Up to 36 months
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Duration of response
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Up to 36 months
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PFS
Time Frame: Up to 36 months
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Progression-free survival
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Up to 36 months
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Survival Rate
Time Frame: Up to 36 months
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Overall Survival Rate
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Up to 36 months
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Vanesa Pons, MD, PhD, Highlight Therapeutics
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
Other Study ID Numbers
- BOT112-02
- 2019-004624-38 (EudraCT Number)
- KEYNOTE-A06 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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