The purpose of this study is to test the safety and efficacy of AUTO4 a CAR T cell treatment
targeting TRBC1 in patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin
The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion
phase. Patients with relapsed or refractory TRBC1 positive selected T-NHL will be enrolled in
both phases of the study. Eligible patients will undergo leukapheresis to harvest T cells,
the starting material for the manufacture of the autologous CAR-T product AUTO4. Following
preconditioning by a chemotherapeutic regimen, the patient will receive AUTO4 intravenously
as a single dose following which they will then enter a 24-month follow-up period
1. Male or female, aged ≥18 years.
2. Willing and able to give written, informed consent to be screened for TRBC1 positive
T-NHL and to enter the main study.
3. Confirmed diagnosis of selected T-NHL, including:
1. Peripheral T cell lymphoma NOS, or
2. Angioimmunoblastic T cell lymphoma, or
3. Anaplastic large cell lymphoma
4. Confirmed TRBC1 positive tumour.
5. Relapsed or refractory disease and have had ≥1 prior lines of therapy.
6. Positron emission tomography (PET)-positive measurable disease per Lugano
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
8. Adequate bone marrow function without the requirement for ongoing blood products and
meets the following criteria:
1. Absolute neutrophil count ≥1.0 x 109/L
2. Absolute lymphocyte count ≥0.5 x 109/L (at entry and prior to leukapheresis).
3. Haemoglobin ≥80 g/L
4. Platelets ≥75 x 109/L
9. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
1. Creatinine clearance (as estimated by Cockcroft Gault) ≥60 cc/min.
2. Serum alanine aminotransferase/aspartate aminotransferase ≤2.5 x upper limit of
3. Total bilirubin ≤25 µmol/L (1.5 mg/dL), except in patients with Gilbert's
4. Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or
multiple gated acquisition (MUGA) cardiac scan, unless the institutional lower
limit of normal is lower.
5. Baseline oxygen saturation ≥92% on room air and ≤Grade 1 dyspnoea.
10. For females of childbearing potential (defined as <2 years after last menstruation or
not surgically sterile), a negative serum or urine pregnancy test must be documented
at screening, prior to pre-conditioning and confirmed before receiving the first dose
of study treatment. For females who are not postmenopausal (<24 months of amenorrhea)
or who are not surgically sterile (absence of ovaries and/or uterus), a highly
effective method of contraception together with a barrier method must be used from the
start of the pre-conditioning stage and for at least 12 months after the last dose of
AUTO4 (study treatment). They must agree not to donate eggs (ova, oocytes) for the
purposes of assisted reproduction during the study and for 12 months after receiving
the last dose of study drug
11. For males, it must be agreed that two acceptable methods of contraception are used
from the start of the pre-conditioning stage and for at least 12 months after the last
dose of AUTO4 (one by the patient - usually a barrier method, and one by the patient's
partner. Also, that sperm will not be donated during the treatment period and for at
least 12 months after the last dose of study treatment.
12. No contra-indications for leukapheresis, or the pre-conditioning regimen.
Patients meeting any of the following exclusion criteria must not be enrolled into the
1. Patients with T cell leukaemia.
2. Females who are pregnant or lactating.
3. Prior treatment with investigational gene therapy or approved gene therapy or
genetically engineered cell therapy product or allogeneic stem cell transplant.
4. Known history or presence of clinically relevant central nervous system (CNS)
pathology. Patients with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the CNS.
5. Current or history of CNS involvement by malignancy.
6. Clinically significant, uncontrolled heart disease
1. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial
fibrillation are not excluded).
2. Evidence of pericardial effusion.
7. Patients with evidence of uncontrolled hypertension or with a history of hypertension
crisis or hypertensive encephalopathy.
8. Patients with a history (within 3 months) or evidence of deep vein thrombosis or
pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of
9. Patients with active gastrointestinal (GI) bleeding.
10. Patients with any major surgical intervention in the last 3 months.
11. Active infectious bacterial, viral disease or fungal disease (hepatitis B virus,
hepatitis C virus, human immunodeficiency virus [HIV], human T cell lymphotropic virus
[HTLV] or syphilis) requiring treatment.
12. Active autoimmune disease requiring immunosuppression.
13. History of other neoplasms unless disease free for at least 2 years (adequately
treated carcinoma in situ, curatively treated non-melanoma skin cancer, breast or
prostate cancer on hormonal therapy are allowed).
14. Prior treatment with programmed cell death protein 1 (PD1), programmed death ligand 1
(PD-L1), or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) targeted therapy, or
tumour necrosis factor (TNF) receptor superfamily agonists including CD134 (OX40),
CD27, CD137 (41BB), and CD357 (glucocorticoid induced TNF receptor family related
protein) within 6 weeks prior to AUTO4 infusion.
15. The following medications are excluded:
1. Steroids: Therapeutic doses of corticosteroids within 72 hours of leukapheresis
or pre-conditioning chemotherapy administration.
2. Cytotoxic chemotherapies within 2 weeks prior to leukapheresis or AUTO4 infusion.
3. Antibody therapy use within 2 weeks prior to AUTO4 infusion, or five half-lives
of the respective antibody, whichever is shorter.
4. Live vaccine within 4 weeks prior to enrolment.
16. Research participants receiving any other investigational agents, or concurrent
biological, chemotherapy, or radiation therapy.
17. Use of rituximab (or rituximab biosimilar) within the last 6 months prior to AUTO4
18. Patients, who in the opinion of the Investigator, may not be able to understand or
comply with the safety monitoring requirements of the study.
For pre-conditioning chemotherapy and AUTO4 Infusion: Patients meeting any of the following
exclusion criteria must not be treated with pre-conditioning chemotherapy or
AUTO4 - and have treatment delayed until they no longer meet these criteria:
1. Severe intercurrent infection at the time of pre-conditioning chemotherapy or the
scheduled AUTO4 infusion.
2. Requirement for supplementary oxygen or active pulmonary infiltrates or significant
deterioration of organ function at the time of pre-conditioning chemotherapy or
scheduled AUTO4 infusion.
3. Significant clinical deterioration of organ functions from screening, as determined by