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

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 nofunctional 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, confirmedhistologically or pathologically documented, and who have previously received andclinically responded to ICI alone or in combination chemotherapy with best responseby RECIST 1.1 being complete response (CR), partial response (PR) or stable disease (SD) who now have progression of disease and have previously received existingstandard of care treatment.

5. Adequate hematologic function, defined by the following:

6. Absolute neutrophil count (ANC) ≥ 1.5 ×10**9/L, without the use of granulocytecolony stimulating factor such as filgrastim within 2 weeks prior to studytreatment.

7. Platelet count ≥ 100 × 10**9/L without transfusion within 2 weeks (≤ 14 days)prior to study treatment.

8. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14days) prior to study treatment.

9. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit ofnormal (ULN), and total bilirubin ≤ 5 × ULN. Exception: Patients who have serumbilirubin increases due to documented underlying Gilbert's Syndrome or familialbenign unconjugated hyperbilirubinemia. Known Hepatitis B and Hepatitis C carriersare eligible if their liver function falls within specifications stipulated here andfor Hepatitis B carriers (HBsAg positive) have low HBV DNA, and for Hepatitis Ccarriers are HCV RNA negative, as well as having adequate disease control onantiviral therapy as required having commenced at least 1 month prior to enrolment.

10. Adequate renal function defined by either a creatinine clearance ≥ 30 mL/min (byCockcroft- Gault formula) or serum creatinine (SCr) < 1.5 × ULN

11. Coagulation tests, defined by the following:

12. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

13. International normalized ratio (INR) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 × ULNis acceptable for patients on Warfarin anticoagulation.

14. Previous antitumor therapy (including endocrine, chemoradiotherapy/ radiotherapy,targeted therapy, or immunotherapy) stopped at least 4 weeks/5 half lives (whicheveris shorter) prior to administration of ACM-CpG. Focal radiation therapy for symptomrelief must have been completed at least 2 weeks prior to the first dose of ACM-CpG.

15. Previous AEs including irAE, have been improved to baseline or Grade ≤ 1 NCI CTCAEv5.0 (except for patients with alopecia, neuropathy, now or other AEs deemed to beG2 but clinically well managed), and specifically prior immune-related adverseevents (irAEs) controlled and improved back to baseline or to Grade ≤ 2 NCI CTCAEv5.0, for example ICI related hypothyroidism requiring repletion with thyroidhormone.

16. Female subjects of childbearing potential should have a negative urine or serumpregnancy within 72 hours prior to receiving the first dose of study medication. Ifthe urine test positive is positive or cannot be confirmed as negative, a serumpregnancy test will be required. Female subjects of childbearing potential should bewilling to use 2 methods of birth control or be surgically sterile or abstain fromheterosexual activity for the course of the study through 26 weeks after the lastdose of the study medication.

17. Male subjects should agree to use adequate method of contraception starting with thefirst dose of study therapy through 26 weeks after the last dose of the studytherapy. Abstinence is acceptable if this is the usual lifestyle and preferredcontraception for the subject.

Exclusion Criteria:

1. Patients receiving granulocyte colony stimulating factor (G-CSF), granulocytemacrophage colony stimulating factor (GM-CSF), erythropoietin, or blood (red bloodcell [RBC] or platelet) transfusion within 14 days prior to the first dose of thestudy drug.

2. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled diabetes asevidenced by screening (baseline) Hb1Ac ≥7.5, asthma, chronic obstructive pulmonarydisease (COPD).

3. Known positive test result for human immunodeficiency virus (HIV) (except thedisease is clinically controlled) or acquired immune deficiency syndrome (AIDS).

4. Patients with any type of primary immunodeficiency or autoimmune disorder requiringtreatment.

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 withinthe last 6 months, uncontrolled angina, viral myocarditis, pericarditis,cerebrovascular accident, or other acute uncontrolled heart disease < 3 months priorto the first dose of the study drug.

9. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first doseof 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 ofthe Investigator might compromise the safety of the patient or integrity of thestudy, interfere with the patient participation in the trial or compromise the trialobjectives.

13. Patients with systemic disease requiring systemic pharmacologic doses ofcorticosteroids greater than 10 mg daily prednisolone (or equivalent) are excluded

• Subjects who are currently receiving steroids at a dose of <= 10 mg daily donot need to discontinue steroids prior to enrollment.

• Subjects that require topical, ophthalmological, and inhalational steroidswould not be excluded from the study.

• Subjects who require active immunosuppression of greater than the steroid dosediscussed above for any reason are excluded.