On December 20, 2022 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, reported results from the Phase 1/2a study of intratumoral cancer vaccine candidate, AGI-134, designed to evaluate the safety and biological activity of AGI-134 in patients with unresectable metastatic solid tumors (Press release, BioLineRx, DEC 20, 2022, View Source [SID1234625437]).
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The study met its primary endpoint of AGI-134’s safety and tolerability. In this first-in-human trial, a total of 38 patients were treated with AGI-134: 5 patients in part 1, the accelerated dose-escalation part of the study; and 33 patients in part 2, the dose expansion part of the study. Part 1 demonstrated that AGI-134 was safe and well tolerated, with no dose-limiting toxicities reported. The maximum tolerated dose was not reached and the recommended dose for part 2 of the study (RP2D) was determined to be up to 200mg. In the dose expansion part 2 of the study, AGI-134 was generally well-tolerated, with treatment-related adverse events being transient and mostly mild to moderate.
Generation of an immune response and markers of clinical efficacy were assessed as secondary endpoints. Most patients analyzed showed an increase in Alpha-Gal antibodies, indicating increased overall immune activity. Additionally, increases in antigen presenting cells (APCs) were observed in most tissue samples analyzed, and T cell and macrophage tumor infiltration was seen in approximately one-third of evaluable patients’ injected tumors, and in approximately half of evaluable patients’ un-injected lesions. Radiological assessments found that 29 percent of patients in the trial achieved best overall response of stable disease. Seven of the 11 patients who achieved stable disease had previously failed checkpoint-inhibitor therapy.
"In this first-in-human, single-agent trial, we were encouraged with AGI-134’s safety profile and the observed initiation of immune activity in patients," said Philip Serlin, Chief Executive Officer of BioLineRx. "We plan to seek publication of our data at a medical congress in 2023, and in consultation with our scientific advisory board, we will determine the next steps for the program in the first half of next year. We want to thank the patients who participated in this important trial, their caregivers, and our physician collaborators."
The Phase 1/2a clinical trial was a multicenter, open-label study, which recruited a total of 38 patients in the UK, Spain and Israel. The study had two parts: part one was an accelerated dose-escalation study in five patients to determine the maximum tolerated dose and the recommended dose for part 2 of the study; part two was a dose expansion study at the recommended dose in 33 patients, designed to evaluate the safety and tolerability of AGI-134, and to validate AGI-134’s mechanism of action using a wide array of biomarkers. For more information on this Phase 1/2a study, see NCT03593226.
PATIENT CHARACTERISTICS
Total enrollment: 38 patients
Gender: 21 Male, 17 Female
Solid Tumor Cancer Type: Melanoma (21), Colon (5), Breast (4), Squamous Cell (3). Sarcoma (2), Cervical Node (1), Endometrial (1), Synovial (1)
ECOG score: 0 to 1 with life expectancy not less than 3 months
SAFETY
AGI-134 was generally well-tolerated, and adverse events (AEs) were mostly transient, mild to moderate in severity
CLINICAL RESPONSE
Best overall response of stable disease (SD) was observed in 29 percent (11/38) of patients according to RECIST1.1 criteria
7 of the 11 patients who achieved stable disease had failed prior checkpoint inhibitor therapy
IMMUNE RESPONSE BIOMARKERS
Increase in Alpha-Gal antibodies
Most patients analyzed showed an increase in Alpha-Gal antibodies as measured by IgG and IgM titers
Tumor infiltration following treatment with AGI-134
59 percent (10/17) of evaluable patients showed an increase in conventional dendritic cells (CD11c+ HLADR+) within or outside of the tumor
29 percent (5/17) of evaluable patients showed an increase in T helper cells (CD3+CD4+) in injected lesions and 47 percent (8/17) in un-injected lesions,
35 percent (6/17) of evaluable patients showed an increase in Cytotoxic T cells (CD3+CD8+) in injected lesions, and 47 percent (8/17) in un-injected lesions
24 percent (4/17) of evaluable patients showed an increase in macrophages (CD68+) in injected lesions and 47 percent (5/17) in un-injected lesions
About AGI-134
AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intra-tumoral administration, thereby targeting the body’s pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient’s own tumor neo-antigens.
AGI-134 has been evaluated in numerous pre-clinical studies. In a mouse melanoma model, treatment with AGI-134 led to regression of established primary tumors and suppression of secondary tumor (metastases) development. Synergy has also been demonstrated in additional pre-clinical studies when combined with an anti-PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 was obtained by BioLineRx through the acquisition of Agalimmune Ltd.