Allogeneic NKG2DL-targeting CAR γδ T Cells (CTM-N2D) in Advanced Cancers (ANGELICA)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age21+
SponsorCytoMed Therapeutics Pte Ltd
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.)
Trial design
Design model
Sequential
Treatments tested in this trial
Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells (CTM-N2D)
Biological/VaccineIn the production of CTM-N2D, blood cells from healthy donors are used as starting materials. Through a proprietary expansion technology, γδ T cells of high-purity can be obtained. These γδ T cells are further grafted with NKG2DL-targeting CARs using mRNA electroporation to enhance its anticancer potency. The finished product (CTM-N2D) are then infused allogeneically into cancer patients.
Treatment groups
12 Participants
are divided into 2 treatment groupsGroup A: Dose-Escalation ArmExperimental treatment 1 intervention
Group B: Optimal Dose ArmExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To determine a dose regimen and schedule of CTM-N2D at which no more than one patient out of up to six patients at the same dose level experience a CTM-N2D-related DLT
Cohort 1: Three patients will be treated with four escalating doses of CTM-N2D to determine an optimal dose based on the incidence of DLT. DLT is defined as an unexpected grade 3 or 4 non-hematologic toxicity that is probably related to CTMN2D infusion and experienced within 8 weeks immediately after the start of study treatment. Treatments with maintenance doses of CTM-N2D will not be considered in determining DLT.
Time frame
Within 8 weeks immediately after the start of study treatment2
Number of Participants With Treatment-Related Adverse Events as assessed by NCI CTCAE v5.0
Cohort 2: Six patients will be treated with four infusions of CTM-N2D at the optimal dose determined in Cohort 1.
Time frame
24 months after the start of study treatmentSecondary outcomes
1
Maximum objective response rate according to RECIST v1.1
Tumour Asessments
Time frame
24 months after the start of study treatment2
Progression-free survival (PFS)
Trial subjects will be followed for survival status, at the discretion of the investigator, from the end of the study until their death, or for a period of up to 48 months after the last patient was initiated for study treatment, whichever occurs first.
Time frame
Up to 48 months after the last patient was initiated for study treatment3
Overall survival (OS)
Trial subjects will be followed for survival status, at the discretion of the investigator, from the end of the study until their death, or for a period of up to 48 months after the last patient was initiated for study treatment, whichever occurs first.
Time frame
Up to 48 months after the last patient was initiated for study treatment4
Duration of response in patients with objective response up to M24 after the start of study treatment (i.e., C1:1D1)
Trial subjects will be followed for survival status, at the discretion of the investigator, from the end of the study until their death, or for a period of up to 48 months after the last patient was initiated for study treatment, whichever occurs first.
Time frame
Up to 48 months after the last patient was initiated for study treatmentOther outcomes
1
Detection and quantification of lymphocyte subsets including γδ T cell subset in blood
CTM-N2D related blood test
Time frame
24 months after the start of study treatment2
Detection and quantification of serum cytokines
CTM-N2D related blood test
Time frame
24 months after the start of study treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
CytoMed Therapeutics Pte Ltd
Lead sponsor
National University Hospital, Singapore
Collaborator
Source ClinicalTrials.gov