Intramuscular ACM-CpG Monotherapy in Patients With Advanced/Metastatic Solid Tumors With Prior Response to Immunotherapy Alone or in Combination With Chemotherapy

NCT06587295 | Recruiting Phase 1

• 1 other identifier: ACMBxNCCS001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor; Metastatic Solid Tumor

Keywords

ACM-CpG

Outcome Measures

Primary Outcomes (13)

• 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.

  28 days (1 cycle)

• 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.

  Up to 2 years.

• Safety of ACM-CpG Monotherapy

  Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters.

  Up to 2 years.

• Tolerability of ACM-CpG Monotherapy

  In terms of dose interruptions, reductions and dose intensity.

  Up to 2 years.

• Incidence of antibody development against PEG

  Up to 2 years.

• Correlations of antibody development against PEG with incidence of AEs

  Up to 2 years.

• Correlations of antibody development against PEG with severity of AEs

  Up to 2 years.

• Correlations of antibody development against PEG with objective response rate (ORR)

  Up to 2 years.

• Objective response rate (ORR)

  Percentage of patients with best overall response of Complete Response or Partial Response, in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST). Summarized by dose level.

  Up to 2 years.

• Disease control rate (DCR)

  Percentage of patients with best overall response of Complete Response or Partial Response or Stable Disease, in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST). Summarized by dose level.

  Up to 2 years.

• Duration of response (DOR)

  The time from the earliest date of documented Complete Response or Partial Response, in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST), until documented disease progression or death (by any cause, in the absence of progression), among the subset of patients who achieve Complete Response or Partial Response. In progression-free patients, DOR will be censored at the time of the last evaluable tumor assessment following the earliest date of documented Complete Response or Partial Response.

  Up to 2 years.

• Progression-free survival (PFS)

  The time from first study treatment until documented disease progression or death (by any cause, in the absence of progression). In progression-free patients, PFS will be censored at the time of the last evaluable tumor assessment (RECIST v1.1 and iRECIST).

  Up to 2 years.

• Overall survival (OS)

  The time from first study treatment to death due to any cause. Patients alive or lost to follow-up will be censored at the last date known to be alive.

  Up to 2 years.

Study Arms (2)

Escalation

EXPERIMENTAL

Drug: Intramuscular ACM-CpG Monotherapy (Escalation)

Expansion

EXPERIMENTAL

Drug: Intramuscular ACM-CpG Monotherapy (Expansion)

Interventions

Intramuscular ACM-CpG Monotherapy (Escalation) DRUG

Dose 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.

Escalation

Intramuscular ACM-CpG Monotherapy (Expansion) DRUG

Patients will be administered ACM-CpG monotherapy at a dose determined in the dose escalation phase.

Expansion

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.
• Adequate hematologic function, defined by the following:
• Absolute neutrophil count (ANC) ≥ 1.5 ×10\*\*9/L, without the use of granulocyte colony stimulating factor such as filgrastim within 2 weeks prior to study treatment.
• Platelet count ≥ 100 × 10\*\*9/L without transfusion within 2 weeks (≤ 14 days) prior to study treatment.
• Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment.
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), and total bilirubin ≤ 5 × ULN. Exception: Patients who have serum bilirubin increases due to documented underlying Gilbert's Syndrome or familial benign unconjugated hyperbilirubinemia. Known Hepatitis B and Hepatitis C carriers are eligible if their liver function falls within specifications stipulated here and for Hepatitis B carriers (HBsAg positive) have low HBV DNA, and for Hepatitis C carriers are HCV RNA negative, as well as having adequate disease control on antiviral therapy as required having commenced at least 1 month prior to enrolment.
• Adequate renal function defined by either a creatinine clearance ≥ 30 mL/min (by Cockcroft- Gault formula) or serum creatinine (SCr) \< 1.5 × ULN
• Coagulation tests, defined by the following:
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• International normalized ratio (INR) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 × ULN is acceptable for patients on Warfarin anticoagulation.
• Previous antitumor therapy (including endocrine, chemoradiotherapy/ radiotherapy, targeted therapy, or immunotherapy) stopped at least 4 weeks/5 half lives (whichever is shorter) prior to administration of ACM-CpG. Focal radiation therapy for symptom relief must have been completed at least 2 weeks prior to the first dose of ACM-CpG.
• Previous AEs including irAE, have been improved to baseline or Grade ≤ 1 NCI CTCAE v5.0 (except for patients with alopecia, neuropathy, now or other AEs deemed to be G2 but clinically well managed), and specifically prior immune-related adverse events (irAEs) controlled and improved back to baseline or to Grade ≤ 2 NCI CTCAE v5.0, for example ICI related hypothyroidism requiring repletion with thyroid hormone.

You may not qualify if:

• 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.
• Major surgery within 4 weeks prior to the first dose of the study drug.
• Pregnant or nursing
• Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation.
• Clinically significant cardiac conditions, including myocardial infarction within the last 6 months, uncontrolled angina, viral myocarditis, pericarditis, cerebrovascular accident, or other acute uncontrolled heart disease \< 3 months prior to the first dose of the study drug.
• Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
• Live viral vaccine therapies within 4 weeks prior to the first dose of study drug.
• Any known, documented, or suspected history of illicit substance abuse.
• Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the Investigator might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the trial or compromise the trial objectives.
• Patients with systemic disease requiring systemic pharmacologic doses of corticosteroids greater than 10 mg daily prednisolone (or equivalent) are excluded
• Subjects who are currently receiving steroids at a dose of \<= 10 mg daily do not need to discontinue steroids prior to enrollment.
• Subjects that require topical, ophthalmological, and inhalational steroids would not be excluded from the study.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• ACM Biolabs: collaborator

Study Sites (1)

National Cancer Centre, Singapore

Singapore, 168583, Singapore

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dr Amit Jain, MBBS, MRCP (UK), MMed

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Amit Jain, MBBS, MRCP (UK), MMed

CONTACT

64368620; amit.jain@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: September 19, 2024
• Study Start: January 15, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)