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

• Status: Recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bioncotech Therapeutics; Highlight Therapeutics
• Treatments: Pembrolizumab

Criteria

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:

1. 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.

2. 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.