Childhood cancer chimeric antigen receptor (CAR) T-cell therapy

Published: October 2023

WHO analysed the current landscape and pipeline of childhood cancer drugs from 2007 through July 2022. This analysis focuses on the chimeric antigen receptor (CAR) T-cell therapy. Products are reported by phase of development and malignancy type. Trials are reported by countries where trials are conducted, WHO Region, income group, and sponsor. See below for details on the scope, analysis, and limitations.

See also:

What you see | Scope, analysis and limitations | Data sources 

What you see

The data visualization shows the:

• Number of CAR T-cell therapy:
  • Highest phase (chart A)
  • Malignancy type (charts B)
• Number of trials on CAR T-cell therapy by:
  • WHO region (chart C.1)
  • Income group (chart C.2)
  • Country (chart C.3)
  • Type of sponsor (chart D.1)
  • Sponsor (chart D.2)
• List of CAR T-cell therapy targets by highest development phase and malignancy type (chart E).
  

Products can also be viewed by grouped phases (select the phases of interest using top left tick boxes).

Note: CAR T-cell therapy can be studied for multiple malignancy types, covered by multiple trials conducted in multiple locations. The numbers displayed in these charts may total to more than the total number of targets or trials.

Points to note:

• Out of 48 targets identified:
  • The most advanced construct development for 54% (26) of all targets are in phase I and 42% (20) are in phase II (chart A). Only a single construct (targeting CD19 for acute lymphoblastic leukaemia) has been approved/marketed for children (select “Marketed “in chart A and see chart E).
  • Acute myeloid leukaemia (22 targets) and acute lymphoblastic leukaemia (13 targets) are the malignancies with the highest number of targets in clinical trials (chart B.2). Altogether, there are 33 targets under investigation for leukaemias, 16 for solid tumours, 8 for lymphomas, and 7 for brain tumours (chart B.1). Note that one target can be studied for multiple malignancies.
• Out of the 306 trials on CAR T-cell therapy:
  • 59% (180 trials) are conducted in the Western Pacific region, followed by the region of the Americas (88; 29%) and the European Region (44; 14%) (chart C.1).
  • 95% of trials are located in upper middle-income countries (167; 55%) or in high income countries (122; 40%) (chart C.2).
  • Trials conducted in China make up 96% (161/167) of the trials in upper middle-income countries and 89% (161/180) of the trials in the Western Pacific region.

To explore the data further

• Select the grouped phases (top left tick boxes) to see the drugs and trials characteristics by these groups.
• Select a specific malignancy type (chart B.2) or any other specific element or combination of elements to display the corresponding data in the other charts. For example, by selecting acute myeloid leukaemia in chart B.2, we can see that 22 targets are studied for this malignancy type, of which 10 (45%) are at phase I (chart A). These 22 targets correspond to 199 trials with most of the trials (130; 65%) conducted in Western pacific region (chart C.1). 
• Hold the ‘Ctrl’ key on your keyboard to select more than one option. For example, in addition to the selection above, by selecting high income in chart C.2, we can see that 20 of the 66 trials conducted in high income countries are done so by pharmaceutical and biotechnology companies(chart D.1).
• Undo a selection by clicking ‘undo’ or ‘reset’ near the bottom of the page or by clicking the same element again.

Scope, analysis and limitations of the data

Scope

• This analysis focuses on CAR T-cell therapy in use in paediatric cancer clinical trials registered over the past 15 years (2007-July 2022).
• Trials were restricted to cancer treatment studies. Registries, biology studies, supportive care studies, psychosocial studies, etc . were excluded. Minimum age of study participants had to be less than 16 years old.
• Data regarding other products than CAR T-cell therapy were also collected and analysed separately and displayed on a different dashboard.  
• Due to the heterogeneity of CAR constructs targeting the same cell surface antigens and lack of clarity in many clinical trial registry entries as to which specific constructs were being utilized, it was not possible to sort trials by individual construct. Therefore, we chose to pool trials targeting the same antigen and conduct a target-focused analysis.
• Clinical trials of CAR T, where a target was not specified in the clinical trial registry, were not included in the analysis.
• The development phase listed was based upon the most advanced phase of development for a specific target, recognizing that different constructs for the same target may be in different stages of development.

Analysis

• Drug lists:
  
  • Drugs were extracted by reviewing the full entries of all relevant trials for childhood cancers registered in the International Clinical Trials Registry Platform (ICTRP)
• Drug details information were collected from the following sources:
  
  • International Clinical Trials Registry Platform (ICTRP) trial entry
  • Clinical information platforms and literatures
  • Drug information embedded in individual protocols
  • Direct communication by email or phone with principal investigator or drug company, where applicable
• Trial detailed information was collected from:
  
  • International Clinical Trials Registry Platform (ICTRP)
   

  Limitations of the data

  • This analysis relies on data available in the public domain or from contacted trial leads or pharmaceutical companies.
  • This analysis does not cover primarily adult cancers that are occasionally seen in children.
  • Specific malignancies included for a target were based upon study inclusion criteria which were sometimes general (e.g., solid tumours) or included a long list of malignancies that qualified, and may not reflect actual trial enrollment.
  • Only CAR T-cell trials with specified targets were included. Specific targets were identified from the trial entry either based upon the construct name and/or the background description.