Trial Title:
Intramuscular ACM-CpG Monotherapy in Patients With Advanced/Metastatic Solid Tumors With Prior Response to Immunotherapy Alone or in Combination With Chemotherapy
NCT ID:
NCT06587295
Condition:
Advanced Solid Tumor
Metastatic Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
ACM-CpG
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Intramuscular ACM-CpG Monotherapy (Escalation)
Description:
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.
Arm group label:
Escalation
Intervention type:
Drug
Intervention name:
Intramuscular ACM-CpG Monotherapy (Expansion)
Description:
Patients will be administered ACM-CpG monotherapy at a dose determined in the dose
escalation phase.
Arm group label:
Expansion
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.
Detailed description:
This is a phase 1, open-label, dose escalation and expansion study of intramuscular
ACM-CpG monotherapy in patients with advanced or metastatic solid tumours. Dose
escalation will be conducted and the RP2D will be determined for ACM-CpG monotherapy for
intramuscular routes of administration. The study will enroll patients who have received
prior immunotherapy as standard of care treatment and have had demonstrable radiological
responses.
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. The RP2D will be defined based on the observation of MTD in a dose
level cohort, to include dose levels below the MTD, or intermediate between the
pre-specified dose levels based on an overall assessment of all safety data, as well as
all available PK and pharmacodynamic data, and documented objective response
observations. RP2D will be a pharmacologically active dose, declared based on an
aggregate of multiple factors including PK data evaluating the safety margin based on
CpG7909 plasma concentrations across a range of dosing levels compared to prior data
(https://pubmed.ncbi.nlm.nih.gov/17696823/) and clinical results.
Dose escalation and expansion will be performed in patients that have previously
responded to immune checkpoint therapy alone or in combination with chemotherapy and who
have already received standard of care treatment. Following the determination of the
RP2D, dose expansion will be performed.
Approximately up to 30 to 40 patients will be enrolled on study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. ≥ 21 years of age at the time of informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no
functional deterioration over the previous 2 weeks.
3. Estimated life expectancy of more than 12 weeks.
4. 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.
5. Adequate hematologic function, defined by the following:
1. 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.
2. Platelet count ≥ 100 × 10**9/L without transfusion within 2 weeks (≤ 14 days)
prior to study treatment.
3. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14
days) prior to study treatment.
6. 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.
7. Adequate renal function defined by either a creatinine clearance ≥ 30 mL/min (by
Cockcroft- Gault formula) or serum creatinine (SCr) < 1.5 × ULN
8. Coagulation tests, defined by the following:
1. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
2. International normalized ratio (INR) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 × ULN
is acceptable for patients on Warfarin anticoagulation.
9. 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.
10. 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.
11. Female subjects of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test positive is positive or cannot be confirmed as negative, a serum
pregnancy test will be required. Female subjects of childbearing potential should be
willing to use 2 methods of birth control or be surgically sterile or abstain from
heterosexual activity for the course of the study through 26 weeks after the last
dose of the study medication.
12. Male subjects should agree to use adequate method of contraception starting with the
first dose of study therapy through 26 weeks after the last dose of the study
therapy. Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
Exclusion Criteria:
1. 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.
2. 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).
3. Known positive test result for human immunodeficiency virus (HIV) (except the
disease is clinically controlled) or acquired immune deficiency syndrome (AIDS).
4. Patients with any type of primary immunodeficiency or autoimmune disorder requiring
treatment.
5. Major surgery within 4 weeks prior to the first dose of the study drug.
6. Pregnant or nursing
7. Prior organ allograft transplantations or allogeneic peripheral blood stem cell
(PBSC)/bone marrow (BM) transplantation.
8. 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.
9. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose
of study drug.
10. Live viral vaccine therapies within 4 weeks prior to the first dose of study drug.
11. Any known, documented, or suspected history of illicit substance abuse.
12. 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.
13. 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.
- Subjects who require active immunosuppression of greater than the steroid dose
discussed above for any reason are excluded.
Gender:
All
Minimum age:
21 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Centre, Singapore
Address:
City:
Singapore
Zip:
168583
Country:
Singapore
Contact:
Last name:
Amit Jain, MBBS, MRCP (UK), MMed
Phone:
64368620
Email:
amit.jain@singhealth.com.sg
Start date:
November 2024
Completion date:
December 2026
Lead sponsor:
Agency:
National Cancer Centre, Singapore
Agency class:
Other
Collaborator:
Agency:
ACM Biolabs
Agency class:
Industry
Source:
National Cancer Centre, Singapore
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06587295
