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Trial registered on ANZCTR


Registration number
ACTRN12622001542785
Ethics application status
Approved
Date submitted
16/11/2022
Date registered
13/12/2022
Date last updated
8/09/2024
Date data sharing statement initially provided
13/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study of Lewis-Y targeting Chimeric Antigen Receptor T-cells given in combination with Nivolumab in Lewis-Y expressing solid tumours.
Scientific title
A Pilot Study Assessing Safety and Tolerability of Lewis Y (LeY) targeting Chimeric Antigen Receptor (CAR) T cells in combination with Nivolumab in Patients With LeY Expressing Solid Tumours
Secondary ID [1] 308370 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Lewis Y Nivo-CAR-T
Linked study record

Health condition
Health condition(s) or problem(s) studied:
LeY Expressing Advanced Solid Tumours 328164 0
Condition category
Condition code
Cancer 325216 325216 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a pilot, single-centre, dose escalation with dose expansion study designed to investigate the safety and tolerability of a single infusion of LeY CAR T cells in combination with nivolumab in patients with LeY positive advanced solid tumours.

To ensure a sufficient yield of T-lymphocytes, patients are to undergo a steady-state apheresis of mononuclear cells (MNC) without influence of recent chemotherapy or growth factors. For the MNC collection an initial apheresis cycle is to be performed to obtain sufficient quantity of cells to generate LeY CAR T cells. This procedure could last approximately 2-4 hours. It is possible that additional apheresis procedures are needed, such as if there are technical issues or if the procedure needs to be stopped early for some reason. The expected yield of cells will be total nucleated cells 2-7 X10^(9) per patient. These cells will be stored in vapour phase liquid nitrogen for subsequent use.

To increase immunosuppression and improve persistence of engineered T-cells, patients will receive a lymphodepleting conditioning chemotherapy regimen before re-infusion of the transduced T-cells. Lymphodepleting conditioning chemotherapy should be initiated so as to finish at least 48 hours prior to LeY CAR T cells administration.
Patients will receive intravenous lymphodepleting conditioning chemotherapy regimen for 3 consecutive days prior to LeY CAR T cell infusion. The lymphodepleting conditioning chemotherapy should be started within 7 days prior to re-infusion of the LeY CAR T cells and must be completed at least 48 hours before the re-infusion of the LeY CAR T cells.

The lymphodepleting conditioning chemotherapy regimen is as follows:
-Fludarabine (25 mg/m^(2) per day) and
-Cyclophosphamide (300mg/m^(2) per day)
Both are to be administrated for 3 consecutive days prior to LeY CAR T cell infusion.

Nivolumab is to be administered as a 30-minute intravenous infusion, on day -1 (the day prior to LeY CAR T cell infusion), day 14, 28 and 42.

There are 3 planned dose levels of LeY CAR T cell that will be evaluated in conjunction with 240 mg of Nivolumab.
LeY CAR T cell dose escalation/de-escalation decisions will be made by the data safety monitoring committee (DSMC). The first dose to be evaluated will be dose level D1 (2 x10^(8) plus up to 6 x 10^(7) labelled cells) and dose escalation will follow a Bayesian Optimal Interval (BOIN) study design to find the MTD for LeY CAR T cells with nivolumab. After each cohort completes the dose limiting toxicity (DLT) observation period, the DSMC will meet and review the available toxicity and dosing information and determine the next dose level for the following cohort of patients and/or identify the recommended phase II dose for the dose-expansion phase.

LeY CAR T Cell Dose Escalation as follows:
Dose level - 1: 1 x10^(8) plus up to 3 x 10^(7) labelled cells
Dose level 1: 2 x10^(8) plus up to 6 x 10^(7) labelled cells
Dose level 2: 5 x10^(8) plus up to 1.5 x 10^(8) labelled cells
Dose level 3: 1 x10^(9) plus up to 3 x 10^(8) labelled cells

The first dose to be evaluated will be dose level D1 and dose escalation will follow a Bayesian Optimal Interval (BOIN) study design to find the maximum tolerated dose (MTD) for LeY CAR T cells with nivolumab. The BOIN design is a novel Bayesian dose-finding method that optimizes patient treatment ethics by minimizing the chance of exposing patients to sub-therapeutic and overly toxic doses as well accelerating the rate of reaching the MTD. The BOIN design is implemented in a simple way similar to the traditional “3+3” design but is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model-based designs. Dose escalation/de-escalation decisions will be made by the DSMC. The target toxicity rate for the MTD is 0.3 and the maximum sample size is 18.
Initially there will be accelerated dose escalation with cohorts of 1 patient. Finally, we will enroll and treat patients in cohorts of size 3.
To guide dose-escalation decisions:
1) if the observed DLT rate at the current dose is less than or equal to 0.236, the next cohort of patients will be treated at the next higher dose level
2) if the observed DLT rate at the current dose is is less than or equal to 0.359, the next cohort of patients will be treated at the next lower dose level.

When the lowest dose is eliminated, stop the trial for safety.

Patients in the expansion phase will be separate to those enrolled in the dose escalation phase. Participants cannot be enrolled in both phases.

All patients in the dose escalation phase will receive one dose of LeY CAR T cells which will be administered (Day 0) via an intravenous infusion given approximately over 30 minutes. Additionally, patients enrolled in the expansion phase of the study, will receive two administrations of LeY CAR T cells. The first dose of LeY CAR T cells will be unlabelled cells and a second intravenous dose of 64Cu-nanoparticle labelled LeY CAR T, approximately 1 hour following the initial LeY CAR T cell infusion. In patients given 64Cu-nanoparticle labelled LeY CAR T cells, a minimum of 10% and a maximum of 30% of the total number of LeY CAR T cells infused will be labelled with the 64Cu nanoparticle. Cells will be labelled with a maximum of 700MBq per patient. The purpose of this markers is to provide a way of tracking T cells in the body.

Once the MTD is defined in the dose escalation phase, if 18 patients have not received LeY
CAR T cells with nivolumab, further recruitment will occur. If 12 patients were treated at the MTD dose in this escalation phase, up to an additional 6 evaluable patients will be accrued to this dose expansion phase for a total of up to 18 patients in both escalation and expansion phases of study of LeY CAR T cells and nivolumab.

Data will be collected using electronic case report forms - eCRFs. The site PI is required to prepare and maintain adequate and accurate medical records designed to record all observations and other data pertinent to the trial for each trial patient. The medical records must contain adequate information to allow for verification of patient identity throughout the trial. Source data must be attributable, legible, contemporaneous, complete, consistent, original and accurate. De-identified copies of data relating to primary end-points and safety (i.e. AEs logs) must be provided to BaCT in accordance with the Site Source Data Verification Checklist for this trial.
Intervention code [1] 324822 0
Treatment: Drugs
Intervention code [2] 324834 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333059 0
To determine the maximum tolerated dose (MTD) of LeY CAR T cells following a single IV infusion of LeY CAR T cells in combination with nivolumab in patients with LeY expressing advanced solid tumours, as determined by assessing the number of dose limiting toxicities (DLTs).
In this study a DLT is defined as:
-Any treatment-emergent Grade 4* or 5 (death) Adverse Events (AEs) related to LeY CAR T cells and/or nivolumab, excluding laboratory values deemed not clinically significant
-Any treatment-emergent Grade 3* AEs related to LeY CAR T cells and/or nivolumab that do not resolve to less than or equal to Grade 2 within 7 days, excluding laboratory values deemed not clinically significant
-Any treatment-emergent Grade 3 or 4 seizure
-Any treatment-emergent autoimmune event greater than or equal to Grade 3

The following expected events will not be considered DLTs:
-Grade 4 infusional AEs that are reversible to less than or equal to Grade 2 in 8 hours
-Grade 3 or 4 fever or febrile neutropenia for less than or equal to 2 weeks
-Grade 3 transaminases for less than or equal to 2 weeks
-Grade 3 or 4 tumour lysis syndrome (TLS) for less than or equal to 2 weeks
-Grade 3 or 4 hypotension (without other cytokines release syndrome (CRS) symptoms) requiring a single vasopressor for support that resolves to less than Grade 3 in less than or equal to 72 hours
-Grade 3 or 4 CRS with hypotension alone requiring a single vasopressor for support (not requiring intubation) that resolves to less than Grade 3 in more than or equal to 72 hours
-Grade 3 chills
-Grade 3 or 4 lymphopenia
-Grade 3 or 4 leukopenia

CAR T-cell toxicity, including CRS and TLS will be managed using the 'CAR-T cell toxicity management clinical procedure' document developed by the Peter MacCallum Cancer Centre, authored by A. Prof Simon Harrison, Director of Clinical Apheresis.
AEs will be documented using Common Terminology Criteria for Adverse Events (CTCAE5.0).
Timepoint [1] 333059 0
DLTs will be assessed from the time of the first dose of nivolumab (day before infusion of LeY CAR T cells; day -1) until 27 days following the infusion of LeY CAR T cells (28 day DLT observation period). Post-infusion (Day 0 being the day of LeY CAR T cells) hospital visits, including blood collections, will occur on day 1,2,3,6,10,14,21,28.
Primary outcome [2] 333086 0
To determine the rate of dose limiting toxicities (DLTs) of a single IV infusion of LeY CAR T cells in combination with nivolumab in patients with LeY expressing advanced solid tumours.

In this study a DLT is defined as:
- Any treatment-emergent Grade 4* or 5 (death) AEs related to LeY CAR T cells and/or nivolumab, excluding laboratory values deemed not clinically significant
- Any treatment-emergent Grade 3 AEs related to LeY CAR T cells and/or nivolumab that do not resolve to less than or equal to Grade 2 within 7 days, excluding laboratory values deemed not clinically significant
- Any treatment-emergent Grade 3 or 4 seizure
- Any treatment-emergent autoimmune event greater than or equal to Grade 3

Note AEs will be graded using Common Terminology Criteria for Adverse Events (CTCAE5.0).
Timepoint [2] 333086 0
DLTs will be assessed from the time of the first dose of nivolumab (day before infusion of LeY CAR T cells; day -1) until 27 days following the infusion of LeY CAR T cells (28 day DLT observation period). Post-infusion (Day 0 being the day of LeY CAR T cells) hospital visits, including blood collections, will occur on day 1,2,3,6,10,14,21,28.
Secondary outcome [1] 415671 0
To assess the anti-tumour activity of LeY CAR T cells in combination with nivolumab.

Endpoint as follows:
-Overall response (OR), defined as the best response to the LeY CAR T cells in combination with nivolumab based on RECIST v1.1. using PET/CT scans and MRI scans if applicable.
Timepoint [1] 415671 0
Evaluations of anti-tumour activity will occur via CT/MRI Scan at: day 28 and day 56 post LeY CAR T cell infusion, week 16 post LeY CAR T cell infusion and every 4 weeks until week 52. CT/MRI scans will be done every 12 weeks after week 52 until disease progression or 5 years after the last patient is registered to the study. Target and non-target lesions will be measured according to RECIST 1.1 criteria.
Secondary outcome [2] 415672 0
To assess persistence of anti-LeY T-cells in peripheral blood by detection (presence/absence) and quantification of LeY transgene in peripheral blood by quantitative polymerase chain reaction (qPCR) at each time point of assessment.
Timepoint [2] 415672 0
Peripheral bloods will be collected: Day 1 of conditioning chemotherapy, pre-LeY CAR T cell infusion (Day 0), day 1,2,3,6,10,14,21,28,42,56, week 12 and every 4 weeks until week 52. Then every 12 weeks after week 52 until the time of disease progression or 5 years after the last patient is registered to the study.
Secondary outcome [3] 416788 0
To assess the anti-tumour activity of LeY CAR T cells in combination with nivolumab.

Endpoint as follows:
-Duration of response, defined as the time from the date of first partial response (PR) or complete response (CR) until the date of disease progression, for those patients who experience a PR or better as assessed by RECIST v1.1 (death is a censoring event) using PET/CT scans and MRI scans if applicable.
Timepoint [3] 416788 0
Evaluations of anti-tumour activity will occur via CT/MRI Scan at: day 28 and day 56 post LeY CAR T cell infusion, week 16 post LeY CAR T cell infusion and every 4 weeks until week 52. CT/MRI scans will be done every 12 weeks after week 52 until disease progression or 5 years after the last patient is registered to the study. Target and non-target lesions will be measured according to RECIST 1.1 criteria
Secondary outcome [4] 416789 0
To assess the anti-tumour activity of LeY CAR T cells in combination with nivolumab.

Endpoint as follows:
-Progression free survival (PFS), defined as the time from the earliest of first dose of nivolumab or LeY CAR T cells to the earliest date of disease progression as assessed by RECIST v1.1 or death using PET/CT scans and MRI scans if applicable
Timepoint [4] 416789 0
Defined from first dose of nivolumab or LeY CAR T cells to the earliest date of disease progression as assessed by RECIST v1.1 or death using PET/CT scans and MRI scans if applicable

Evaluations of anti-tumour activity will occur via CT/MRI Scan at: day 28 and day 56 post LeY CAR T cell infusion, week 16 post LeY CAR T cell infusion and every 4 weeks until week 52. CT/MRI scans will be done every 12 weeks after week 52 until disease progression or 5 years after the last patient is registered to the study. Target and non-target lesions will be measured according to RECIST 1.1 criteria.
Secondary outcome [5] 416791 0
To assess the anti-tumour activity of LeY CAR T cells in combination with nivolumab.

Endpoint as follow:
-Overall survival (OS) defined as the time from first dose of nivolumab or LeY CAR T cells to date of death
Timepoint [5] 416791 0
Overall survival (OS) defined as the time from first dose of nivolumab or LeY CAR T cells to date of death

Eligibility
Key inclusion criteria
1. Patient has provided written confirmation of informed consent on participant information and consent form (PICF)
2. Patients with an advanced solid tumour (defined as incurable locally advanced or metastatic disease and excluding any haematologic malignancy) Patients who are eligible for PBS-reimbursed PD1 or PD-L1 inhibitors must have received this prior to study enrolment
3. Tumour is positive for LeY expression by immunohistochemistry (IHC) defined as a staining of greater than or equal to 10 % of tumour cells positive for LeY expression
4. Patient is at least 18 years of age at the time of consent
5. Patient has an ECOG performance status of 0-1
6. Life expectancy of greater or equal to 12 weeks
7. Patient has adequate organ function satisfying all of the following:
-Bilirubin less than or equal to 1.5x upper limit of normal (ULN) unless patient has known Gilbert’s syndrome, then less than or equal to 3x ULN
-AST/ALT less than or equal to2.5 x ULN except in patients with known liver metastases where AST/ALT less than or equal to 5.0 x ULN
-Serum creatinine less than 1.5x ULN or creatinine clearance greater than 50ml/min. Creatinine clearance is either derived using the Cockcroft-Gault formula or may be measured by 24 hour urine collection or nuclear medicine assessment
-Adequate pulmonary function defined by SaO2 greater than 91% on room air and less than or equal to grade I dyspnoea
-Left ventricular ejection fraction (LVEF) greater than or equal to 40% as confirmed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA)
-Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10^(9)/L
-Absolute lymphocyte count greater than or equal to 0.5 x 10^(9)/L
-Platelets greater than or equal to 100 x 10^(9)/L
-Haemoglobin greater than or equal to 80g/L
-White cell count (WCC) less than 30 x 10^(9)/L
8. Patient is deemed capable and willing to undergo the planned study procedures in the view of the Investigator
9. Patient has measurable disease as per RECIST 1.1
10. For patients undergoing the (64)^Cu SPION imaging:
a. Patient must pass institutional MRI safety questionnaire
b. Patient must not exceed physical limitations of scanner (weight greater than 105kg and/or height greater than 185cm)
c. Patient must feel they are able to tolerate proposed imaging sequences (e.g. Patient must not suffer from severe claustrophobia or other condition that would prevent them from undergoing MRI)
d. Patients must not have a known allergy to nickel or palladium
11. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
12. Female patients of childbearing potential must be willing to commit to either abstaining continuously from heterosexual intercourse or agree to practice 2 methods of reliable birth control simultaneously. Where one of the methods is a highly effective method of contraception (failure rate of less than 1% per year when used consistently and correctly; see examples below) and one other effective method (i.e., male latex or synthetic condom, diaphragm, or cervical cap) and patient must agree to remain on both methods from the time of signing the patient information and consent form (PICF) until at least 1 year after receiving LeY CAR T cell therapy. Reliable contraception is indicated even where there has been a history of infertility, unless it is due to hysterectomy. Women of childbearing potential (WOCBP) should be referred to a qualified provider of contraceptive methods, if needed. Examples of highly effective contraceptives include:
-User-independent methods: 1) implantable progestogen-only hormone contraception associated with inhibition of ovulation; 2) intrauterine device; intrauterine hormone-releasing system; 3) vasectomised partner
-User-dependent method: progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable)
Woman of childbearing potential are those who have not been surgically sterilized or have not been free from menses related to menopause for greater than 1 year
13. Male patients must commit either to abstaining continuously from heterosexual intercourse or a man who is sexually active with a woman of childbearing potential or a pregnant woman must agree to use a barrier method of contraception from the time of
signing the PICF until at least 1 year after receiving LeY CAR T cell therapy, even if they have undergone a successful vasectomy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with known active central nervous system (CNS), involvement by malignancy. [N.B. Patients with previously treated and/or neurologically stable disease (asymptomatic brain metastases not requiring steroid treatment) will be eligible]
2. Prior CAR T cell therapy
3. Patient has been given chemotherapy and/or granulocyte-colony stimulating factor (G-CSF) within 4 weeks of study registration or is planned to receive such therapy prior to apheresis of PBMC. Patients can only receive cytotoxic drugs as per the schedule of treatment for this protocol
4. Patient has had immunosuppressive therapy within 4 weeks of apheresis. Therapeutic doses of steroids (defined as greater than 10 mg/day of Prednisolone (or equivalent)) must be able to be stopped within 7 days prior to leukapheresis and 72 hours prior to LeY CAR T cell infusion. Physiologic doses of steroid (e.g. Prednisolone less than 10mg or equivalent), topical and inhaled steroids are permitted
5. Patients who are eligible for potentially curative therapy
6. Uncontrolled active or latent Hepatitis B (HBV) or active Hepatitis C (HCV) or HIV
7. Patients with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate treatment
8. A presence of active clinically relevant CNS pathology such as epilepsy, aphasia, severe brain injury, dementia, Parkinson’s disease, cerebellar disease or psychosis
9. Radiation therapy within 2 weeks prior to registration
10. Patient has an active other haematologic or solid malignancy with the exception of superficial BCC or SCC
11. Patient has a history of significant pulmonary disease (including radiation pneumonitis) or known, biopsy proven autoimmune inflammatory disease of the gastrointestinal tract
12. Unstable angina or myocardial infarct within 6 months prior to screening
13. Patient has known clinically significant autoimmune disease
14. Women who are pregnant or breastfeeding
15. Patient has a serious uncontrolled medical disorder, psychological or social factors that which would impair their ability to receive protocol therapy and follow up in the opinion of the investigator
16. Receipt of live attenuated vaccination within 30 days of registration
17. Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis, tuberculosis, or primary immunodeficiency
18. Have a history of allergy to study drug components, or a history of severe hypersensitivity reaction to any mAb

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The first dose to be evaluated will be dose level D1 and dose escalation will follow a Bayesian Optimal Interval (BOIN) study design to find the MTD for LeY CAR T cells with nivolumab. The BOIN design is a novel Bayesian dose-finding method that optimizes patient treatment ethics by minimising the chance of exposing patients to sub-therapeutic and overly toxic doses as well accelerating the rate of reaching the MTD. The BOIN design is implemented in a simple way similar to the traditional “3+3” design but is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model-based designs.

Dose escalation/de-escalation decisions will be made by the DSMC. The target toxicity rate for the MTD is 0.3 and the maximum sample size is 18.

Initially there will be accelerated dose escalation with cohorts of 1 patient. Finally, we will enrol and treat patients in cohorts of size 3. To guide dose-escalation decisions, if the observed DLT rate at the current dose is less than or equal to 0.236, the next cohort of patients will be treated at the next higher dose level; if it is less than or equal to 0.359, the next cohort of patients will be treated at the next lower dose level.
When the lowest dose is eliminated, stop the trial for safety.

The trial design follows three steps:
1. Perform accelerated titration of LeY CAR T cells as follows: treat the first patient at dose level 1. If no DLT is observed, escalate the dose to the next higher level. Continue this one-patient-per-dose escalation process until the first DLT is observed or the highest dose level is reached, and then treat additional 2 patients at the dose that the first DLT is observed or the highest dose if no DLT is observed in all doses. Patients may be treated at lower or intermediate dose levels at the disecretion of the DSMC. Hereafter, patients are treated in cohorts of size 3 as described in steps 2 and 3.
2. To assign a dose to the next cohort of patients, conduct dose escalation/de-escalation according to the following rules:
a. "Eliminate" means that we eliminate the current and higher doses from the trial to prevent treating any future patients at these doses because they are overly toxic.
b. When we eliminate a dose, automatically de-escalate the dose to the next lower level. When the lowest dose is eliminated, stop the trial for safety. In this case, no dose should be selected as the MTD.
c. If none of the actions (i.e., escalation, de-escalation or elimination) is triggered, we treat the new patients at the current dose.
d. If the current dose is the lowest dose and the rule indicates dose de-escalation, treat the new patients at the lowest dose unless the number of DLTs reaches the elimination boundary, at which point terminate the trial for safety.
e. If the current dose is the highest dose and the rule indicates dose escalation, treat the new patients at the highest dose.
3. Repeat step 2 until the maximum sample size of 18 is reached or stop the escalation if the number of patients treated at the current dose reaches 12.

Once the MTD is defined in the dose escalation phase, if 18 patients have not received LeY CAR T cells with nivolumab, further recruitment will occur. If 12 patients were treated at the MTD dose in this escalation phase, up to an additional 6 evaluable patients will be accrued to this dose expansion phase for a total of up to 18 patients in both escalation and expansion phases of study of LeY CAR T cells and nivolumab.

Only 1 patient can be treated with LeY CAR T cells at any given time point during the dose escalation. A new dose level may not be started until patients have completed the DLT observation period and the DSMC has declared the dose level open.
A minimum interval of 14 days has been implemented between the infusion of LeY CAR T cells between the most recent and the next patient within a dose level to allow for assessment of acute AEs associated with the LeY CAR T cells in combination with nivolumab during the dose escalation phase.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
For all endpoints the analysis population will comprise all eligible patients who receive the T-cell infusion and nivolumab.

Patients enrolled in this study will be part of one of two groups of patients:
-Dose escalation for LeY CAR T cells with nivolumab
-Dose expansion for LeY CAR T cells with nivolumab

Dose escalation phase for LeY CAR T cells and nivolumab: The sample size has been determined to allow completion of the escalation phase with 1-3 patients per cohort, up to 12 patients for a dose level.

Dose expansion phase for LeY CAR T cells and nivolumab: Following determination of the MTD for LeY CAR T cells with nivolumab, further patients will be accrued up to a total of 18 patients to be treated with LeY CAR T cells and nivolumab.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Early cessation of study due to manufacturing failure of patient CarT cells.
Date of first participant enrolment
Anticipated
10/01/2023
Actual
17/01/2023
Date of last participant enrolment
Anticipated
12/06/2025
Actual
25/01/2024
Date of last data collection
Anticipated
12/06/2030
Actual
19/02/2024
Sample size
Target
18
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23523 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 38936 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 312614 0
Hospital
Name [1] 312614 0
Centre for Cellular Immunotherapy, Peter MacCallum Cancer Centre
Country [1] 312614 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street, Melbourne Victoria 3000
Country
Australia
Secondary sponsor category [1] 314228 0
None
Name [1] 314228 0
Address [1] 314228 0
Country [1] 314228 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311935 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 311935 0
305 Grattan Street, Melbourne Victoria, 3000 Australia
Ethics committee country [1] 311935 0
Australia
Date submitted for ethics approval [1] 311935 0
28/03/2022
Approval date [1] 311935 0
09/11/2022
Ethics approval number [1] 311935 0

Summary
Brief summary
The main purpose of this study is to test the safety of a new cancer therapy targeting the tumour marker Lewis Y (‘Lewis Y Chimeric Antigen Receptor T-cell Therapy’) in combination with the commonly used cancer drug nivolumab for the treatment of patients with Lewis Y-expressing solid tumours.

Who is it for?
You may be eligible to join this study if you are aged 18 years or older, you have an advanced incurable or metastatic cancer and your cancer expresses the marker Lewis Y on tumour biopsy.

Study details

All participants will receive treatment with Lewis Y Chimeric Antigen Receptor T-cell Therapy and nivolumab.

Prior to treatment, participants will have blood collected to generate the T-cells required for treatment. Participants will then follow a chemotherapy regimen designed to reduce the number of the body’s T cells so that the newly generated T-cells can be administered. This will involve intravenous infusions of the drugs fludarabine and cyclophosphamide once per day for 3 consecutive days in the week prior to T-cell therapy.

Patients enrolled in this study will be part of one of two groups of patients:
-Dose escalation for LeY CAR T cells with nivolumab
-Dose expansion for LeY CAR T cells with nivolumab

The dose escalation phase is when different doses (total number of cells infused) of the cell therapy will be tested. Each participant will receive one dose only by intravenous infusion. The doses tested will be increased or decreased for additional participants enrolled until a safe dose is determined. This safe dose will then be used for the dose expansion phase, where participants may receive up to two doses of cells infused one hour apart by intravenous infusion. Nivolumab will be administered to all participants by intravenous infusion on the day prior to T-cell therapy, and on days 14, 28, and 42 after T-cell therapy.

During the follow-up phase, beyond the first 8 weeks (day 56) post-infusion, imaging and blood tests will occur once a month up to one year post-infusion then every 3 months thereafter for long-term follow-up to the full study period of 5 years.

It is hoped that Lewis Y Chimeric Antigen Receptor T-cell therapy in combination with nivolumab is safe, tolerable, and effective for the treatment of advanced solid cancers expressing the Lewis Y marker. This study will also help to define the dose of T-cell therapy that may be used for treatment of similar individuals in future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122898 0
Prof Benjamin Solomon
Address 122898 0
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne,
Victoria 3000
Country 122898 0
Australia
Phone 122898 0
+61 03 8559 7902
Fax 122898 0
Email 122898 0
[email protected]
Contact person for public queries
Name 122899 0
Benjamin Solomon
Address 122899 0
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne Victoria 3000
Country 122899 0
Australia
Phone 122899 0
+61 03 8559 7902
Fax 122899 0
Email 122899 0
[email protected]
Contact person for scientific queries
Name 122900 0
Benjamin Solomon
Address 122900 0
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne Victoria 3000
Country 122900 0
Australia
Phone 122900 0
+61 03 8559 7902
Fax 122900 0
Email 122900 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Pending sponsor approval.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AILow-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models2023https://doi.org/10.1038/s41467-023-40852-3
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