Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies

Study Overview
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Brief Summary
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This Phase 1, first-in-human (FIH), open-label study is designed to assess the safety, tolerability, and preliminary clinical efficacy of repeated intravenous (IV) infusions of SUPLEXA monotherapy in subjects with measurable metastatic solid tumours and haematologic malignancies

Detailed Description
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This is a FIH Phase 1, non-comparative, open-label, basket-design study. The study will consist of 2 cohorts: Solid tumours cohort Haematologic malignancies cohort: Subjects must fulfill entry criteria and have relapsed or refractory advanced malignancy for which no standard therapy exists. An Data Safety Monitoring Committee (DSMB) will provide oversight of the study and will monitor safety on a regular basis throughout the study to make recommendations on any modifications. The study will be comprised of 3 periods. Screening, Treatment and Follow-up. All eligible subjects will receive minimally 3 weekly dosing of SUPLEXA. Subjects will be monitored closely at the clinic after each weekly infusion. After completion of the first 3 weekly SUPLEXA the treatment period of SUPLEXA may be extended to every 2 weeks until all SUPLEXA is depleted.

Official Title
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A Phase 1, First-in-Human, Open-label Single Agent Study of SUPLEXA Therapeutic Cells in Patients With Metastatic Solid Tumours and Haematologic Malignancies

Conditions
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Oncology

Intervention / Treatment
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* Biological: SUPLEXA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age Adult subjects at least 18 years of age at the time of signing the PICF. Type of Subject and Disease Characteristics Solid Tumours Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumour. Have 1 or more tumours measurable based on RECIST v1.1 as assessed by the local site Investigator. Radiographic scans should be obtained within 4 weeks of Screening. Lesions situated in a previously irradiated area are considered measurable if objective progression has been demonstrated following radiation to such lesions. Subjects who did not attain a durable response after receiving at least one standard/approved therapies which may include chemotherapy, targeted agents, radio-, immuno- conjugates, check point inhibitors or where there is no approved therapy. This includes subjects who attained a long-term stable disease (SD), or partial response (PR) are eligible. Long term SD subjects on a checkpoint inhibitor may continue checkpoint inhibitor (CPI) therapy. Haematologic malignancies Histologically or cytologically confirmed multiple myeloma, lymphoma, and chronic lymphocytic leukemia (collectively termed as haematologic malignancies for the purposes of this protocol) which has relapsed or is refractory advanced malignancy for which no curative standard therapy exists. Exclusion Criteria: Medical Conditions Known central nervous system (CNS) metastases and/or carcinomatous meningitis. Prior allogeneic transplant. Diagnosis of immunodeficiency or is receiving chronic and non-physiological, systemic steroid therapy or any other form of immunosuppressive therapy. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy at screening or Day 1. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator. Any unresolved Grade 2 or greater reversible toxicity from a previous anticancer therapy except for alopecia or Grade 2 neuropathy. Clinically significant cardiovascular disease, including any of the following: Stroke or myocardial infarction within 6 months prior to first dose in the study. Presence of unstable angina within 6 months prior to first dose in the study. Congestive heart failure of New York Heart Association Grade 2 or higher. History or presence of clinically significant ventricular arrhythmias, or conduction abnormality; presence of clinically significant atrial fibrillation and resting bradycardia. Corrected QT interval (QTcF) of >450 msec (males) or >470 msec (females) using Fridericia's correction formula. History of congenital long QT syndrome. Known history of testing positive for human immunodeficiency virus (HIV), and/or positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection. A serious non-malignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor. At high risk of developing TLS per (Cairo, 2010)). Specifically: Burkitt's lymphoma ALL with LDH > 2xULN or WBC >100 x 109 per µL. AML with WBC >100 x 109 per µL. Any other condition that, in the opinion of the Investigator, would prohibit the subject from effectively participating in the study. Diagnostic Assessments A performance status ≥2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (solid tumours cohort) or Karnofsky performance scale of ≥60 (haematologic malignancies cohort) Does not demonstrate adequate organ function as defined as an excursion beyond the acceptable limits below. All screening laboratories should be performed at screening and on the day of first administration of study therapy. Prior radiotherapy within 2 weeks of start of study intervention. Subjects must have recovered from all radiation-related toxicities and not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. Transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (CSF) (including granulocyte CSF [GCSF], granulocyte-macrophage CSF [GMCSF], or recombinant erythropoietin) within 4 weeks prior to baseline. Any vaccines (live, attenuated, inactivated or research vaccines) within 30 days of dosing with study intervention (refer to Section 6.8.1 for prohibited vaccines). Prior/Concurrent Clinical Study Experience Participation in another clinical study of an investigational agent during the 2 weeks of this study's screening. Other Exclusions < 6 months life expectancy at the local site Investigator judgement. Pregnant or breastfeeding female subjects within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.

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: non-comparative, open-label, basket-design study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SUPLEXA<br>autologous cellular therapy comprised predominantly of NK, NK-T, and T cells stored in cryogenic media | Biological: SUPLEXA<br>* PBMC-derived autologous cellular therapy derived through an ex vivo activation procedure, resulting in a cell mixture comprised predominantly of NK, NK-T, and T cells stored in cryogenic media.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability of SUPLEXA in subjects with malignant solid tumour and haematologic malignancies. | Incidence of dose limiting toxicities measured by Incidence of adverse events and serious adverse events overall, by severity, by relationship to each study intervention, and those that led to discontinuation of study intervention. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solid tumours cohort: To assess the efficacy of SUPLEXA in subjects with malignant solid tumour as assessed by the Investigator based on response evaluation criteria in solid tumours (RECIST) v1.1 or by changes in tumour-derived blood biomarkers. | Objective response rate defined as the proportion of subjects with best overall response of either a complete response or partial response measured by Time to Progression (TTP) | 24 months | 
| Haematologic malignancies cohort: To assess the efficacy of SUPLEXA in subjects with haematologic malignancies (multiple myeloma, lymphoma and chronic lymphocytic leukemia). | Objective response rate as defined by standard of care. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous therapy, cellular therapy, T cell, NK-T cell, gamma delta T cell, CTL, PBMC-derived effector cells, NK cells