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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I Open-Label Dose Escalation Study Of Intravenous INKmune In Patients With Myelodysplastic Syndrome With Excess Blasts (MDS-EB-1/2 - MDS-CMML 1/2) Or Acute Myeloid Leukaemia (AML)

Conditions
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Cancer, MDS-EB, Myelodysplastic Syndromes, Acute Myeloid Leukemia, AML

Intervention / Treatment
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* Biological: INKmune


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years old. Subjects with: 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. Subjects with AML in complete remission (or complete remission with incomplete count recovery) unsuitable for intensive chemotherapy or allogeneic stem cell transplantation. Subjects with relapsed MDS or AML post-allogeneic stem cell transplant, with slowly progressive disease unsuitable for intensive chemotherapy. Subject has adequate organ and marrow function (as defined below): Serum creatinine ≤ 1.5 X ULN, or measured creatinine clearance ≥ 60 ml/min/1.73m2. Aspartate aminotransferase (AST) and ALT levels ≤ 3 X ULN. Total bilirubin < 1.5 X ULN, unless known diagnosis of Gilbert's syndrome. Absolute neutrophil (ANC) ≥ 500/mm3; 0.5 x 109/L Platelet count ≥ 50,000/mm3; 50 x 109/L Haemoglobin ≥ 100mg/L (transfusion to obtain haemoglobin ≥ 100mg/L within 24 hours prior to dosing is allowed). 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. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 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. Subject, must be able to understand and voluntarily sign a written informed consent, and are willing and able to comply with the protocol requirements. Subject must have a life expectancy greater than 3 months in the opinion of the PI. Exclusion Criteria: Subject diagnosed with any other sub-classification of MDS. Subject is currently receiving cancer-specific treatment with the exceptions of supportive treatments such as bisphosphonate or steroid treatments for symptomatic control. Subject has had prior NK cell targeting therapy. Subject has a current requirement for steroids > 10 mg daily; prednisolone or equivalent. Subject has impaired cardiac function or clinically significant cardiac disease including the following: New York Heart Association grade III or IV congestive heart failure. Myocardial infarction within the last 6 months prior to dosing with INKmune Impaired left ventricular ejection fraction (LVEF < 40%) as assessed according to institutional standards. 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. Subject has known allergy to any of the formulation components of INKmune. 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. 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. Subject is pregnant or is currently breastfeeding. Subject has uncontrolled seizures as determined by the PI. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 in addition to supportive care. Three cohorts, comprised of at least 3 participants, are planned. Each participant will be screened up to 28 days prior to treatment. After participants have received all doses, they will be reviewed at Day 29 and Day 43 and then followed up with monthly clinic appointments for the following 3 months (Days 73 and 119) for clinical assessment and blood tests. Once Day 119 visit is completed this classifies end of study for the participant. The trial will end after data collection has been completed for each trial participant.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Schedule of Assessments<br>INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15. In Cohort 1, the initial planned dose is 1 x 10^8 INKmune; In Cohort 2, the weekly dose will increase to 3 x 10^8 INKmune; In Cohort 3, the weekly dose will increase to 5 x 10^8 INKmune. | Biological: INKmune<br>* INKmune is a patented biologic delivery system and method for cancer treatment using in vivo priming and activation of natural killer (NK) cells in order to achieve tumor cell lysis. INKmune is a suspension of INB16 cells which have been rendered replication incompetent. INKumne is a replication-incompetent tumor cell line that does not require donor matching.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective 1 | Identify the incidence and seriousness of AEs and their relationship (causality) to INKmune as graded by NCI CTCAE criteria v.5.0. | 2-3 years | 
| Primary Objective 2 | Identify a RP2D of INKmune. The RP2D is defined as the maximum tolerated dose (MTD) of the agent which will be defined as the dose at which the complication rate is less than 33%. | 2-3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Objective 1 | To assess the overall response rate by measuring changes in percentage blasts in PB at days 29, 43, 73, 119 and BM at day 29. | 1-2 years | 
| Secondary Objective 2 | To assess the overall response rate, partial response rate or complete response rate in subjects administered INKmune using the WHO criteria by measuring changes in vital signs, electrocardiogram (ECG), and safety laboratory parameters throughout the study. | 3-4 years | 
| Secondary Objective 3 | To assess the progression-free survival (PFS) time defined as time to increase in transfusion dependence and or increase in percentage blasts in Peripheral Blood (PB) and/or Bone Marrow (BM). | 2-3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, AML, NK Cell Based Therapy, Immune Based Therapy