A Phase I Open-Label Dose Escalation Study of Intravenous INKmune In Patients With MDS or AML

INMB-INB16-002 is a Phase I open-label, dose escalation study of INKmune therapy in subjects with myelodysplastic syndrome (MDS) with excess blasts without Auer rods (EB-1 or 2, or CMML 1 or 2) or subjects with acute myeloid leukaemia (AML) in complete remission.

INMB-INB16-002 is a Phase 1 open-label, dose escalation study of INKmune therapy in subjects with MDS with excess blasts without Auer rods (EB-1 or 2, or CMML 1 or 2) who have completed treatment with Azacytidine (AZA) and not achieved complete remission (CR) and who are not thought to be fit for intensive chemotherapy, or subjects with AML in complete remission (or complete remission with incomplete count recovery) unsuitable for intensive chemotherapy or allogeneic stem cell transplantation or subjects with relapsed MDS or AML post-allogeneic stem cell transplant with slowly progressive disease unsuitable for intensive chemotherapy.

Eligibility Criteria:
Inclusion Criteria:

1. Subject is ≥ 18 years old.
2. Subjects with:

   1. MDS-EB-1/2, MDS-CMML 1-2 who have completed treatment with Azacytidine (AZA), and not achieved complete remission (CR) who are not thought to be fit for intensive chemotherapy.
   2. Subjects with AML in complete remission (or complete remission with incomplete count recovery) unsuitable for intensive chemotherapy or allogeneic stem cell transplantation.
   3. Subjects with relapsed MDS or AML post-allogeneic stem cell transplant, with slowly progressive disease unsuitable for intensive chemotherapy.
3. Subject has adequate organ and marrow function (as defined below):

   1. Serum creatinine ≤ 1.5 X ULN, or measured creatinine clearance ≥ 60 ml/min/1.73m2.
   2. Aspartate aminotransferase (AST) and ALT levels ≤ 3 X ULN.
   3. Total bilirubin \< 1.5 X ULN, unless known diagnosis of Gilbert's syndrome.
   4. Absolute neutrophil (ANC) ≥ 500/mm3; 0.5 x 109/L
   5. Platelet count ≥ 50,000/mm3; 50 x 109/L
   6. Haemoglobin ≥ 100mg/L (transfusion to obtain haemoglobin ≥ 100mg/L within 24 hours prior to dosing is allowed).
4. Subject must be at least 21 days from previous anticancer therapy (eg, chemotherapy, radiation therapy, immunotherapy and monoclonal antibodies, or investigational therapeutic agents) at the time of study screening and meet criteria in "3" above.
5. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. a. Sexually active female subjects of childbearing potential must agree to use a highly effective method of contraception for the duration of study therapy and for 3 months after the last dose of INKmune. Acceptable forms of contraception methods are as follows:

   * Non-hormonal methods (i.e. intrauterine device, IUD)
   * have vasectomised partner (the vasectomised partner must be the sole partner of the trial participant and have received medical assessment of its surgical success)
   * True sexual abstinence Women of childbearing potential must discontinue any hormonal forms of birth control at least 4 weeks prior to first study dosing and commence using a highly effective, non- hormonal method as described above. Any pregnancy that occurs for study participants should be monitored for potential side effects.

     b. Male subjects with partners who are of childbearing potential must agree a double barrier method of contraception i.e. condom with either cap or diaphragm for the duration of study therapy and for 3 months after the last dose of INKmune. Male subjects with partners who are pregnant must use a condom for the same duration to avoid INKmune exposure to developing foetus. Note: Subjects who are abstinent (defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatments), must agree to remain abstinent for the study duration and for 3 months after the last study dose of INKmune. The reliability of sexual abstinence will be evaluated in relation to the preferred and usual lifestyle of the subject.
7. Subject, must be able to understand and voluntarily sign a written informed consent, and are willing and able to comply with the protocol requirements.
8. Subject must have a life expectancy greater than 3 months in the opinion of the PI.

Exclusion Criteria:

1. Subject diagnosed with any other sub-classification of MDS.
2. Subject is currently receiving cancer-specific treatment with the exceptions of supportive treatments such as bisphosphonate or steroid treatments for symptomatic control.
3. Subject has had prior NK cell targeting therapy.
4. Subject has a current requirement for steroids \> 10 mg daily; prednisolone or equivalent.
5. Subject has impaired cardiac function or clinically significant cardiac disease including the following:

   1. New York Heart Association grade III or IV congestive heart failure.
   2. Myocardial infarction within the last 6 months prior to dosing with INKmune
   3. Impaired left ventricular ejection fraction (LVEF \< 40%) as assessed according to institutional standards.
6. Subject has shown lack of recovery of prior AEs to Grade ≤1 severity (NCI CTCAE v5.0) (except alopecia) due to therapy administered prior to the initiation of study drug dosing. Stable persistent grade 2 peripheral neuropathy may be allowed as determined on a case-by-case basis at the discretion of the PI and Medical Monitor.
7. Subject has known allergy to any of the formulation components of INKmune.
8. Subjects has active, severe infection requiring systemic treatment. Subjects may become eligible once infection has resolved and they are at least seven days from completion of antibiotics.
9. Subject concomitant use of complementary or alternative medication or other agents (investigational therapeutic agents) will not be allowed without approval of a PI or sub- investigator (SI). Every effort will be made to maximize subject safety and minimize changes in chronic medications.
10. Subject is pregnant or is currently breastfeeding.
11. Subject has uncontrolled seizures as determined by the PI.
12. Subject has any other condition or finding that in the opinion of the PI or Sponsor Medical Monitor may render the subject at excessive risk for treatment complications or may not be able provide evaluable outcome information.