Oncology
Conditions
Keywords
autologous therapy, cellular therapy, T cell, NK-T cell, gamma delta T cell, CTL, PBMC-derived effector cells, NK cells
Brief summary
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
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.
Interventions
BIOLOGICALSUPLEXA
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.
Sponsors
Alloplex Biotherapeutics Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
non-comparative, open-label, basket-design study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 1. Adult subjects at least 18 years of age at the time of signing the PICF. Type of Subject and Disease Characteristics Solid Tumours 2. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumour. 3. 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. 4. 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 5. 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 1. Known central nervous system (CNS) metastases and/or carcinomatous meningitis. 2. Prior allogeneic transplant. 3. Diagnosis of immunodeficiency or is receiving chronic and non-physiological, systemic steroid therapy or any other form of immunosuppressive therapy. 4. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy at screening or Day 1. 5. 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. 6. Any unresolved Grade 2 or greater reversible toxicity from a previous anticancer therapy except for alopecia or Grade 2 neuropathy. 7. Clinically significant cardiovascular disease, including any of the following: 1. Stroke or myocardial infarction within 6 months prior to first dose in the study. 2. Presence of unstable angina within 6 months prior to first dose in the study. 3. Congestive heart failure of New York Heart Association Grade 2 or higher. 4. History or presence of clinically significant ventricular arrhythmias, or conduction abnormality; presence of clinically significant atrial fibrillation and resting bradycardia. 5. Corrected QT interval (QTcF) of \>450 msec (males) or \>470 msec (females) using Fridericia's correction formula. 6. History of congenital long QT syndrome. 8. 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. 9. 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. 10. At high risk of developing TLS per (Cairo, 2010)). Specifically: 1. Burkitt's lymphoma 2. ALL with LDH \> 2xULN or WBC \>100 x 109 per µL. 3. AML with WBC \>100 x 109 per µL. 11. Any other condition that, in the opinion of the Investigator, would prohibit the subject from effectively participating in the study. Diagnostic Assessments 12. 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) 13. 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. 14. 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. 15. 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. 16. 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 17. Participation in another clinical study of an investigational agent during the 2 weeks of this study's screening. Other Exclusions 18. \< 6 months life expectancy at the local site Investigator judgement. 19. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of SUPLEXA in Subjects With Malignant Solid Tumour and Haematologic Malignancies. | 24 months | 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. Note: due to patient availability, only solid tumour patients were enrolled |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 24 months | Objective response rate defined as the proportion of subjects with best overall response of either a complete response (CR) or partial response (PR) measured by Time to Progression (TTP). Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR), is defined as at least 30% decrease in the sum of the longest diameter of target lesions. |
Countries
Australia
Participant flow
Recruitment details
Participants were recruited from CANCER RESEARCH SA, Greenslopes Private Hospital/Gallipoli Medical Research Foundation and Southern Oncology Clinical Research Unit in Australia starting April 2022 to January 2024.
Participants by arm
| Arm | Count |
|---|---|
| SUPLEXA Autologous, non-engineered cellular therapy comprised of lymphoid cells activated through a proprietary ex vivo procedure. A cryogenically stored product was prepared for all eligible participants to receive this adoptive immune cell therapy | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | did not receive treatment | 3 |
| Overall Study | screen failure-did not receive treatment | 8 |
Baseline characteristics
| Characteristic | SUPLEXA |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age of Participants | 64 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Ethnicity of participants Asian | 4 Participants |
| Ethnicity of participants White | 31 Participants |
| Region of Enrollment Australia | 35 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 25 / 35 |
| serious Total, serious adverse events | 6 / 35 |
Outcome results
Primary
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. Note: due to patient availability, only solid tumour patients were enrolled
Time frame: 24 months
Population: Intent to Treat Population (all participants allocated intervention) were assessed for adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUPLEXA | Safety and Tolerability of SUPLEXA in Subjects With Malignant Solid Tumour and Haematologic Malignancies. | Numer of Subjects reporting TEAE related to study intervention | 3 Participants |
| SUPLEXA | Safety and Tolerability of SUPLEXA in Subjects With Malignant Solid Tumour and Haematologic Malignancies. | Number of Subjects reporting any Treatment Emergent Adverse Events | 25 Participants |
| SUPLEXA | Safety and Tolerability of SUPLEXA in Subjects With Malignant Solid Tumour and Haematologic Malignancies. | Number of Subjects with TEAE leading to discontinuation of study intervention | 2 Participants |
Secondary
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 (CR) or partial response (PR) measured by Time to Progression (TTP). Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR), is defined as at least 30% decrease in the sum of the longest diameter of target lesions.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUPLEXA | 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. | 3 Number of participants: ORR |