This article is for informational purposes only and does not constitute medical advice. All decisions regarding pediatric cancer treatment and clinical trial participation should be made in partnership with a qualified pediatric oncologist. Seek care at a Children's Oncology Group (COG) member institution for access to the full range of available trials.
Summary
Pediatric cancer is fundamentally different from adult cancer — it arises from different cell types, is driven by distinct genetic alterations, and requires treatments designed for developing bodies. In 2026, childhood cancer survival rates have improved dramatically (overall 5-year survival now above 85% for many diagnoses), but significant challenges remain for relapsed/refractory acute leukemia, diffuse intrinsic pontine glioma (DIPG), and aggressive solid tumors. Clinical trials are central to pediatric oncology — it is estimated that over 60% of children with cancer participate in a clinical trial at some point in their care, far higher than the adult rate of ~5%. The Children's Oncology Group (COG) coordinates the largest network of pediatric cancer trials in the world. This guide covers the most active areas of 2026 pediatric cancer research and how families can access them.
The Children's Oncology Group (COG)
COG is the world's largest pediatric cancer research organization, consisting of over 200 member institutions across the U.S., Canada, Europe, and Australia. When a child is diagnosed with cancer at a COG member institution, their oncologist can offer enrollment in COG protocols — which are institutional clinical trials that in many cases represent the national standard of care for newly diagnosed patients, not just experimental last resorts.
- Finding a COG center: The COG website (childrensoncologygroup.org) lists all member institutions — parents should seek care at a COG center from diagnosis to maximize trial access.
- Active COG studies in 2026 span ALL, AML, brain tumors, neuroblastoma, Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and lymphoma.
- Protocol types: Frontline treatment protocols (newly diagnosed), salvage protocols (relapsed/refractory), biology studies (no treatment change, contributes tumor specimens), and follow-up/survivorship studies.
CAR-T Cell Therapy for Childhood Leukemia
Tisagenlecleucel (Kymriah) was the first FDA-approved CAR-T therapy, authorized in 2017 for children and young adults (up to age 25) with relapsed/refractory B-cell ALL. By 2026, it has treated thousands of patients with complete remission rates of approximately 81% in the pivotal ELIANA trial. The landscape has since expanded significantly.
- Second-generation CD19 CAR-T: Axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi) are being evaluated in pediatric populations after adult approvals; clinical trials comparing different CAR-T constructs are ongoing.
- CD22-targeted CAR-T: Some B-ALL tumors relapse by losing CD19 expression; CD22-directed CAR-T (and dual CD19/CD22 products) are in Phase 1/2 trials to address antigen-escape relapse.
- T-cell ALL: CAR-T for T-lineage leukemia faces the fratricide problem (T-cells killing each other); engineered allogeneic (donor) CART products and gene-edited approaches are in early trials.
- Bridging therapy trials: Studies examining how to best bridge patients to CAR-T infusion while minimizing pre-treatment toxicity that could impair T-cell quality for manufacturing.
DIPG and Pediatric Brain Tumors
Diffuse Intrinsic Pontine Glioma (DIPG) — now recognized as a subtype of Diffuse Midline Glioma (DMG) characterized by H3K27M mutation — has historically been one of pediatric oncology's most devastating diagnoses, with median survival of approximately 9–11 months. In 2026, for the first time, there are genuinely promising treatments entering trials.
- ONC201 (dordaviprone): A DRD2/DRD3 antagonist and ClpP agonist showing remarkable activity against H3K27M-mutant DMG; Phase 3 ACTION trial (NCT05580562) is now the landmark study — ONC201 gained accelerated approval for recurrent H3K27M+ DMG in April 2024 and Phase 3 is testing it frontline after radiation.
- GD2-directed CAR-T for DIPG: MSKCC Phase 1 trial (NCT04196413) using intracranial CAR-T delivery targeting GD2 antigen; preliminary results show tumor regression in some patients with extended survival — recruiting at specialist centers.
- Convection-enhanced delivery (CED): Trials delivering drugs directly into the brainstem via catheter to bypass the blood-brain barrier; combining with immunotoxins and checkpoint inhibitors.
- Medulloblastoma: COG ACNS1422 and successor studies test risk-stratified therapy and proton beam radiation; molecular subgrouping (Group 3/4, WNT, SHH) now guides treatment intensity decisions.
NTRK Inhibitors for Pediatric Solid Tumors
NTRK gene fusions (involving NTRK1, NTRK2, or NTRK3) occur across many tumor types and are particularly common in certain pediatric cancers. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) — TRK inhibitors — are FDA-approved for TRK fusion-positive solid tumors regardless of tumor type, histology, or patient age. Response rates are approximately 75–80% in TRK fusion-positive tumors.
- Tumor types with high NTRK fusion rates: Infantile fibrosarcoma (~90%), secretory breast carcinoma, mammary analog secretory carcinoma, congenital mesoblastic nephroma, and pontine glioma subtypes.
- Next-generation TRK inhibitors: Selitrectinib (LOXO-195) and repotrectinib target TRK resistance mutations that emerge after first-generation TRK inhibitor therapy; pediatric expansion cohorts are enrolling.
- Testing requirement: Comprehensive genomic profiling (RNA-based fusion testing preferred over DNA) is necessary to identify NTRK fusions — not all standard next-generation sequencing panels detect them.
Neuroblastoma and Other Solid Tumors
High-risk neuroblastoma remains a significant challenge despite intensive multimodal treatment (surgery, high-dose chemotherapy, autologous stem cell transplant, immunotherapy with dinutuximab, and isotretinoin). Active 2026 trials include:
- ANBL1232 (COG): Testing tandem autologous transplant vs single consolidation in high-risk neuroblastoma; long-term follow-up from this landmark trial is being analyzed.
- GD2-targeted therapy: Naxitamab (Danyelza, anti-GD2 antibody) approved for relapsed/refractory high-risk neuroblastoma; combination trials with immunotherapy and DFMO (difluoromethylornithine) maintenance are ongoing.
- Ewing sarcoma: Phase 2 trials evaluating lurbinectedin, cabozantinib, and oncolytic viruses for relapsed Ewing — a disease with no approved second-line treatment.
- Osteosarcoma: Persistence of the same chemotherapy backbone for 40 years has prompted AOST trials of cabozantinib + nivolumab and other combinations; OS remains one of the most under-researched pediatric cancers.
How Families Access Pediatric Cancer Trials
- Seek care at a COG member institution from the time of diagnosis — most community hospitals are not equipped to run COG protocols. Request a second opinion at a major children's cancer center (St. Jude, CHOP, Children's Hospital of Los Angeles, Dana-Farber/Boston Children's, etc.) if your local hospital is not a COG member.
- Molecular profiling: Request comprehensive genomic profiling of the tumor at diagnosis — this identifies targetable alterations (NTRK, ALK, ROS1, BRAF, etc.) that determine eligibility for targeted therapy trials.
- St. Jude Cloud and PBTA: Pediatric Brain Tumor Atlas and similar data-sharing initiatives help match patients to trials by identifying rare alterations.
- Alex's Lemonade Stand Foundation: Funds pediatric cancer research and provides patient navigation services including a clinical trial finder specific to pediatric oncology.
- ClinicalTrials.gov: Search by condition and filter by age range (e.g., "child: 1 year to 17 years") + "recruiting" to find active pediatric trials.