Allogeneic NKG2DL-targeting CAR γδ T Cells (CTM-N2D) in Advanced Cancers (ANGELICA)

Recruiting now · Phase 1

Conditions studied: Cancer, Malignancy, Refractory Cancer, Relapsed Cancer

In brief

CAR-T is a pioneering cancer treatment which has found success in some cancers. This treatment is made first by taking blood cells from the patient. Then in the lab, an artificial protein - a Chimeric Antigen Receptor (CAR), is grafted on the surface of immune cells. The modified cells, which are readministered to the patient, have enhanced abilities to target and destroy cancers than unmodified immune cells. Currently approved CAR-T can only be used autologously. i.e. the patient will receive CAR-T treatment made from their own cells. This is because current CAR-T treatment uses αβ T cells - a type of immune cell which are largely non-transferable between individual human beings due to the high risk of Graft-versus-Host Disease. However, autologous CAR-T comes with many limitations. A lengthy, manufacturing process follows after the patient donates their own blood, accompanied by a high risk of manufacturing failure, which can be attributed to the cell quality from cancer patients undergoing stressful anti-cancer therapy. CytoMed Therapeutics pioneers a new CAR-T treatment (CTM-N2D) which may confer some benefit over current CAR-T treatment. CTM-N2D uses a subtype of immune cell -- γδ T cell. Secondly, the CAR on CTM-N2D targets a surface antigen called NKG2DL which are commonly present in many cancer. These two features may confer a safer product profile, of better quality and may be efficacious in cancers where previous CAR-T treatments has not. The phase I clinical trial of CTM-N2D will be conducted at the National University Hospital, Singapore. The objective of this clinical trial is to determine the optimal dose of CTM-N2D, and to investigate its safety and tolerability. The subjects of the clinical trial will also be investigated for their tumour response to CTM-N2D. CTM-N2D has undergone preclinical studies. Relevant data from other clinical trials are also used to infer the expected outcome, and strategies of management of this clinical trial. The institution's ethical review board must give its approval before the study may begin. An independent Data Safety Monitoring Board monitors the safety aspect of this trial.

Key facts

Study ID: NCT05302037
Run by: CytoMed Therapeutics Pte Ltd
People needed: 12
Starts: 2024-11-19
Expected to finish: 2026-12-01
Last updated by the study team: 2024-11-22

Who can join

Age: 21 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

At least 21 years of age
Provision of signed and dated, written informed consent prior to any study specific procedures, sampling, and analyses (if applicable, the written informed consent may include access to all archival tumour tissue, e.g., diagnostic and/or most recent samples for correlative study)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and an estimated life expectancy of greater than 12 weeks
Females of reproductive age group must be on effective contraception (if sexually active), must not be breast feeding and must have a negative pregnancy test prior to the start of lymphodepletion.
For the duration of the study and for 1 week after the last study drug administration, sexually active male patients must be willing to use barrier contraception (i.e., condoms) with all sexual partners. Where the sexual partner is a 'woman of child-bearing potential' who is not using effective contraception, the male patients must use a condom (with spermicide) during the study and for 6 months after the last dose of a study drug.
Adequate hepatic, renal and lung function as demonstrated by any of the following laboratory values:
AST or ALT ≤ 3 x ULN
Total bilirubin ≤ 1.5 x ULN
Glomerular filtration rate (GFR) > 50 mL/min, as assessed using the Cockroft-Gault formula or 24 h urine creatinine collection
SpO2 on room air > 94%
Adequate bone marrow reserve as demonstrated by any of the following laboratory values:
Absolute neutrophil count (ANC) ≥ 1.0x10\^9/L
Platelet count ≥ 75 x 10\^9/L
Haemoglobin ≥ 9.0 g/dL
Patients must have a metastatic cancer resistant to or deemed unsuitable for at least two standard lines of cancer therapy regimens, as part of their management of recurrent/persistent disease.
Presence of measurable tumour by RECIST 1.1 criteria
Serum 25 Hydroxyvitamin D total ≥ 20ng/ml
Have a diagnosis of cancer that is known to express NKG2D ligands

You may not qualify if…

With the exception of alopecia, any unresolved toxicities from prior therapy ≥ the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 2
Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to the start of lymphodepletion
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection including any patient known to have human immunodeficiency virus (HIV) or hepatitis virus. Screening for chronic conditions is not required.
All HBsAg-positive patients (For HBsAg-negative, but anti-HBc total-positive patients, HBV viral load will be further tested. If HBV viral load is negative, patients may be included.)
Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
Subjects with vitiligo or alopecia
Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Subjects without active disease in the last 5 years may be included but only after consultation with the medical monitor
Subjects with celiac disease controlled by diet alone
For other autoimmune or inflammatory conditions not specifically mentioned, discuss on case-by-case basis with investigator and medical monitor
Concurrent severe and/or uncontrolled medical condition (e.g., severe COPD, severe Parkinson's disease, active inflammatory bowel disease) or psychiatric condition (screening for chronic disease is not required)
Female patients who are breast-feeding or patients of reproductive potential who are not employing an effective method of contraception
Receiving, or having received during the four weeks prior the start of lymphodepletion, any investigational product
Treatment with any investigational biological product (e.g., immune check point blockers, antibodies, nanoparticles, experimental) during the four weeks prior the start of lymphodepletion
Patients who underwent major surgery during the four weeks prior to the start of lymphodepletion
Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) during the three weeks prior to the start of Lymphodepletion
Active infection requiring systemic long-term (> 2 weeks) treatment with antibiotics, antifungal or antiviral drugs
Cardiac dysfunction as defined as: Myocardial infarction within six months of study entry, NYHA Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias or reduced LVEF < 50%.
Any of the following cardiac criteria:
Mean resting corrected QT interval (QTc) > 470 msec
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)
Uncontrolled hypertension requiring clinical intervention
Failed dental clearance (for zoledronic acid administration)
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements

Where it is running

National University Hospital — Singapore, Singapore (enrolling)

Full record on ClinicalTrials.gov

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