Five key studies into drugs for childhood cancers

Childhood Cancer Awareness Month

DDW’s Diana Spencer highlights five key clinical studies taking a new therapeutic approach to childhood cancers.

Over 100 subtypes of childhood cancer exist today and it represents the most common cause of disease-related death in children. However, despite the fact that children’s response to adult cancer drugs is often poor, due to the challenges of developing medicines for this population, only six drugs are made specifically for childhood cancer.1

There are a number of challenges faced in paediatric R&D, including the fact that the overall group includes five different age groups, the need for specific biomarkers, the extra length of time needed for trials, and the ethical concerns of conducting clinical trials in children.2,3 There are additional challenges in childhood cancer, as a large proportion of the genetic drivers in paediatric cancer do not overlap with those of adult cancers, and childhood tumours are often exceptionally rare.4

Recent regulatory initiatives in the United States and Europe have aimed to increase the study of novel anti-cancer therapies in children.5 The Research to Accelerate Cures and Equity (RACE) for Children Act of 2017 authorised the Food and Drug Administration (FDA) to require paediatric clinical trials for new oncology drugs with relevant molecular targets and has a had a positive impact on the number of drugs approved in paediatric indications.6

In 2022, the FDA approved azacitidine (Vidaza) for juvenile monomyelocytic leukaemia, brentuximab vedotin (Adcetris) for Hodgkin lymphoma, and atezolizumab (Tecentriq), the first PD-L1 inhibitor approved for a paediatric sarcoma. However, paediatric oncology still remains an area of huge unmet need and low investment, and represents an opportunity for drug developers to make a meaningful  impact.7

To mark Childhood Cancer Awareness Month, here we take a look five key clinical studies taking a new therapeutic approach to childhood cancers that will hopefully lead to breakthrough treatments in the coming years.

  1. Ibrutinib/indoximod combination platform

Dr David Munn and Dr Theodore Johnson of the Medical College of Georgia at Augusta University are launching a Phase I trial to investigate if the addition of ibrutinib can promote anti-tumour activity in brain cancer patients who are actively progressing, and have already become resistant to chemoimmunotherapy with indoximod alone.

If the trial is successful, the ibrutinib/indoximod platform would readily transfer to other tumours and chemotherapy. This could have profound impacts on end-stage patients who have previously had little or no treatment options.

The trial is being funded through a CureSearch Catapult Award, which supports Phase I or Phase II clinical trials that advance promising therapies for paediatric cancer.

Read more: CureSearch to fund Phase I clinical trial for paediatric brain cancer

  1. The international AcSé-ESMART trial

A combination of the PARP inhibitor olaparib and the investigational ATR inhibitor ceralasertib has shown clinical benefit in paediatric patients with solid tumours exhibiting DNA replication stress and/or DNA repair deficiencies, according to results from the Phase I portion of the Phase I/II AcSé-ESMART trial.

The researchers believe that paediatric cancers have a kind of primary resistance to PARP inhibitors and that combination with an ATR inhibitor could potentially overcome this.

AcSé-ESMART is an international European proof-of-concept platform trial intended to match paediatric, adolescent, and young adult patients with relapsed or treatment-refractory cancers with a treatment regimen targeted to their cancer’s mutational profile.

Read more: Combo therapy may benefit some paediatric cancer patients

  1. Targeting TGF-ß

Kristen VanHeyst of University Hospitals Rainbow Babies & Children’s Hospital’s Angie Fowler Adolescent & Young Adult Cancer Institute, has received a CureSearch Young Investigator Award to find immunotherapeutic options for osteosarcoma.

Although overall survival rates for osteosarcoma are improving, there have been no significant improvements in survival outcomes for patients with metastatic pulmonary osteosarcoma – it is hoped the project could offer viable treatment for these patients.

In the study, Dr VanHeyst will target the molecule TGF-ß, which is produced by osteosarcoma cells and immune cells in the tumour microenvironment and dampens the ability of the patient’s immune system to eradicate the tumour.

Read more: CureSearch to fund new study for aggressive paediatric bone cancer

  1. The MYC gene in osteosarcoma

In June 2023, Dr Patrick Grohar of Children’s Hospital of Philadelphia was awarded a $1.5 million grant to develop a new targeted treatment approach for paediatric osteosarcoma.

The Fight Osteosarcoma Together Super Grant is a joint funding award with St Baldrick’s Foundation, CureSearch, Battle Osteosarcoma, Michael and April Egge, The Osteosarcoma Collaborative, and the Zach Sobiech Osteosarcoma Fund of Children’s Cancer Research Fund.

Dr Grohar’s team will study the role of the MYC gene, a common gene in osteosarcoma tumours, and determine how MYC makes osteosarcoma aggressive.

Read more: $1.5 million awarded for osteosarcoma research

  1. Transcription factor inhibitors

Talus Bio has received $4.3 million in new grants from the National Institutes for Health (NIH) and the Washington State Andy Hill CARE Fund to advance its paediatric cancer therapeutics.

The Seattle-based company received two grants totalling $2.3M from the CARE Fund to fuel the discovery of new transcription factor inhibitors for rhabdomyosarcoma and neuroblastoma, two childhood cancers.

Read more: $4.3 million awarded to advance transcription factor drugs



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