Safety and Tolerability of AGI-134
Research type
Research Study
Full title
A phase I/IIa, multicentre, open label study designed to evaluate the safety and tolerability of AGI-134 as monotherapy and in combination with pembrolizumab, in unresectable metastatic solid tumours
IRAS ID
251148
Contact name
Shimrit Yefet
Contact email
Sponsor organisation
Agalimmune Ltd.
Eudract number
2018-001032-22
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 1 months, 18 days
Research summary
Research Summary:
AGI-134 (alpha-Gal) is a synthetic molecule that can trigger a systemic (all over the body) anti-tumour response when injected into a tumour deposit.
This study will evaluate the safety, tolerability and efficacy of AGI-134 given alone and in combination with pembrolizumab in patients with unresectable metastatic solid tumours. Unresectable solid tumours are cancers that cannot be removed completely through any combination of surgery, radiation therapy or drug treatment.This study is divided to 2 parts:
Part 1 will assess in a small group of patients the safety and tolerability of increasing doses of AGI-134 injected intra-tumourally (IT) and will determine the maximum AGI-134 dose that can be tolerated.
Part 2 will assess the safety, tolerability and clinical effect of the dose selected in part 1 in a group of patients who will receive AGI-134 alone injected intra-tumourally and in a group of patients who will receive AGI-134 in combination with Pembrolizumab, an established immunotherapy drug.Summary of study results:
AGI-134 (alpha-Gal) is a synthetic molecule that can trigger a systemic (all over the body) anti-tumour response when injected directly into a tumour. The primary purpose of this study is to evaluate the safety and tolerability of the experimental drug AGI-134 in the treatment of unresectable/metastatic solid tumours. Unresectable solid tumours are cancers that cannot be removed completely through any combination of surgery, radiation therapy or drug treatment. Metastatic tumours refer to cancer cells that have moved from the place where they first formed to another part of the body.
This study was divided into 2 parts:
Part 1 assessed in a small group of patients the safety and tolerability of increasing doses of AGI-134 injected intratumourally (IT) into superficial tumours, and determined the maximum AGI-134 dose that can be tolerated.
Part 2 assessed the safety, tolerability and clinical effect of the dose selected in Part 1 in a group of patients with unresectable/metastatic tumours, who received AGI 134 injected intratumourally into superficial or deep lesions.Summary and Conclusions:
A total of 38 subjects enrolled in the study and received treatment with AGI-134, including five subjects who were enrolled in Part 1 of the study. In Part 1 of the study subjects were dosed up to 200 mg, without reaching the maximum tolerated dose. Therefore, the recommended Part 2 dose was set at 200 mg, and the actual volume the subjects received was based on the size of the injected tumour.
Thirty subjects (78.9%) reported adverse events thought to be related to the study drug (side effects). The most common adverse events which occurred in ≥10% of the patients and were considered related to the drug were fatigue, injection site pain, vomiting, shortness of breath, and itchiness. No concerns were raised by physical examination or vital sign measurements with respect to the study treatment. No differences were apparent in the nature or severity of the adverse events reported between the different injected volumes.
Overall, the safety profile of AGI-134 was found to be acceptable and expected based on the AGI-134 mechanism of action and the intratumoural injection procedure.Summary of Results:
AGI-134 (alpha-Gal) is a synthetic molecule that can trigger a systemic (all over the body) anti-tumour response when injected directly into a tumour. The primary purpose of this study is to evaluate the safety and tolerability of the experimental drug AGI-134 in the treatment of unresectable/metastatic solid tumours. Unresectable solid tumours are cancers that cannot be removed completely through any combination of surgery, radiation therapy or drug treatment. Metastatic tumours refer to cancer cells that have moved from the place where they first formed to another part of the body.
This study was divided into 2 parts:
Part 1 assessed in a small group of patients the safety and tolerability of increasing doses of AGI-134 injected intratumourally (IT) into superficial tumours, and determined the maximum AGI-134 dose that can be tolerated.
Part 2 assessed the safety, tolerability and clinical effect of the dose selected in Part 1 in a group of patients with unresectable/metastatic tumours, who received AGI 134 injected intratumourally into superficial or deep lesions.Summary and Conclusions:
A total of 38 subjects enrolled in the study and received treatment with AGI-134, including five subjects who were enrolled in Part 1 of the study. In Part 1 of the study subjects were dosed up to 200 mg, without reaching the maximum tolerated dose. Therefore, the recommended Part 2 dose was set at 200 mg, and the actual volume the subjects received was based on the size of the injected tumour.
Thirty subjects (78.9%) reported adverse events thought to be related to the study drug (side effects). The most common adverse events which occurred in ≥10% of the patients and were considered related to the drug were fatigue, injection site pain, vomiting, shortness of breath, and itchiness. No concerns were raised by physical examination or vital sign measurements with respect to the study treatment. No differences were apparent in the nature or severity of the adverse events reported between the different injected volumes.
Overall, the safety profile of AGI-134 was found to be acceptable and expected based on the AGI-134 mechanism of action and the intratumoural injection procedure.REC name
South Central - Oxford B Research Ethics Committee
REC reference
18/SC/0497
Date of REC Opinion
19 Nov 2018
REC opinion
Further Information Favourable Opinion