ACM-CpG is a CpG-B TLR9 agonist, which in animal models has led to shrinkage and complete disappearance of injected tumors, durable antitumor memory, and growth inhibitory effects on non-injected tumors while intramuscular administration led to durable control of tumors. This Phase I trial will assess the safety and early signs of efficacy of intramuscular injection of ACM-CpG in patients with advanced malignant solid tumors.
The overall objectives of this trial are to establish the safety ACM-CpG.
≥ 21 years of age at the time of informed consent.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no functional deterioration over the previous 2 weeks.
Estimated life expectancy of more than 12 weeks.
Patients with terminal, Stage 4, advanced or metastatic solid tumors, confirmed histologically or pathologically documented, and who have previously received and clinically responded to ICI alone or in combination chemotherapy with best response by RECIST 1.1 being complete response (CR), partial response (PR) or stable disease (SD) who now have progression of disease and have previously received existing standard of care treatment.
Patients receiving granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, or blood (red blood cell [RBC] or platelet) transfusion within 14 days prior to the first dose of the study drug.
Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled diabetes as evidenced by screening (baseline) Hb1Ac ≥7.5, asthma, chronic obstructive pulmonary disease (COPD).
Known positive test result for human immunodeficiency virus (HIV) (except the disease is clinically controlled) or acquired immune deficiency syndrome (AIDS).
Patients with any type of primary immunodeficiency or autoimmune disorder requiring treatment.
Sequential
Intramuscular ACM-CpG Monotherapy (Escalation)
DrugDose escalation for ACM-CpG monotherapy administered via intramuscular injection will similarly be conducted using traditional 3+3 dose escalation. Three dose levels have been planned. If the patient experiences a DLT or two Grade ≥ 2 drug-related toxicity, the dose level will be expanded according to a 3+3 design. The safety and tolerability of each dose level will be assessed by the study team after all patients enrolled in the dose level have been followed for at least 21 days after the first dose of the ACM-CpG (DLT observation period). Once the MTD is reached, the RP2D will be determined.
Intramuscular ACM-CpG Monotherapy (Expansion)
DrugPatients will be administered ACM-CpG monotherapy at a dose determined in the dose escalation phase.
Maximum tolerated dose (MTD)
Highest dose level at which less than one-third of the patients in the dose level experienced dose limiting toxicities (DLTs) during the first cycle of treatment.
Recommended phase 2 dose (RP2D)
To be determined based on the MTD or the totality of the safety and efficacy data if the MTD is not reached.
Safety of ACM-CpG Monotherapy
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters.
Tolerability of ACM-CpG Monotherapy
In terms of dose interruptions, reductions and dose intensity.
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National Cancer Centre, Singapore
Lead sponsor
ACM Biolabs
Collaborator
