Study of BO-112 With Pembrolizumab for Colorectal or Gastric/GEJ Cancer With Liver Metastasis

NCT04508140 | Terminated Phase 2 Results DMC

• 3 other identifiers: BOT112-022019-004624-38KEYNOTE-A06
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 12

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 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.

Conditions

Colorectal Cancer; Gastric Cancer; Oesophageal Cancer

Outcome Measures

Primary Outcomes (2)

• 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

  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)

  from baseline to approximately 8 months

Secondary Outcomes (5)

• Disease Control Rate Based on RECIST 1.1

  from baseline to approximately 8 months

• Objective Response Rate Based iRECIST

  from baseline to approximately 8 months

• Disease Control Rate Based on iRECIST

  from baseline to approximately 8 months

• Progression-free Survival

  from baseline to approximately 8 months

• Overall Survival Rate

  at 6 months from enrolment

Study Arms (2)

Cohort A

EXPERIMENTAL

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

EXPERIMENTAL

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

Interventions

Hepatic Biopsy PROCEDURE

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.

Cohort A; Cohort B

BO-112 with pembrolizumab DRUG

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®

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Highlight Therapeutics: lead

Study Sites (12)

Institut Jules Bordet

Brussels, Belgium

Location

UCL St-Luc

Brussels, Belgium

Location

University Hospital Antwerp (UZA)

Edegem, Belgium

Location

Universitair Ziekenhus Gent

Ghent, Belgium

Location

IRCCS Ospedale Policlinico San Martino

Genova, Italy

Location

Azienda Ospedaliera Ospedale Niguarda Ca'Granda

Milan, Italy

Location

Hospital Reina Sofía

Córdoba, Cordoba, Spain

Location

Hospital Valle Hebrón

Barcelona, Spain

Location

Hospital Gregorio Marañón

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Spain

Location

Hospital Clínico de Valencia

Valencia, Spain

Location

Related Publications (1)

• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

  PMID: 35623069 DERIVED

Related Links

• Company web site

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms; Esophageal Neoplasms

Interventions

BO-112; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Results Point of Contact

• Title: Marisol Quintero
• Organization: Highlight Therapeutics S.L.

mquintero@highlighttherapeutics.com

+34 961 10 99 55

Study Officials

• Vanesa Pons, MD, PhD

  Highlight Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, non-comparative study.

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 11, 2020
• Study Start: June 17, 2020
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: November 29, 2024
• Results First Posted: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6); BE (4); IT (2)