New CAR T-Cell Immunotherapy Approaches to Solid Tumors in Children

New chimeric antigen receptor (CAR) T-cell immunotherapies are offering hope for patients with hematologic malignancies. However, that is not the case with solid tumors. Researchers in Seattle are hoping to change that, having just announced the start of a CAR T-cell immunotherapy trial for children and young adults with relapsed or refractory non–central nervous system, epidermal growth factor receptor (EGFR)-expressing solid tumors. In the phase I STRIvE-01 trial, CAR T cells will target the EGFR protein expressed in many childhood sarcomas, kidney tumors, and neuroblastomas.

“Our CAR is generated using an EGFR antibody that has been shown to effectively target EGFR on tumors while sparing EGFR-expressing normal tissues. We hypothesize that using CD19 as a second target, which is expressed on all normal B cells, will enhance expansion and persistence of the infused CAR T cells,” said Katie Albert, MD, of Seattle Children’s Hospital and lead investigator for the STRIvE-01 trial.

Albert said the phase I, open-label, non-randomized study with 36 patients will examine the safety and feasibility of administering autologous peripheral blood–derived T cells that have been genetically modified using a self-inactivating lentiviral vector to express an EGFR-specific CAR alone or in combination with a CD19-specific driver CAR.

Anticipating that it will take a multifaceted approach to overcome solid tumors, STRIvE-01 will include two sequential treatment arms. In the first arm, patients will receive EGFR806 CAR T cells to first evaluate the toxicity and establish the maximum tolerated dose of the experimental therapy. Once the first arm is complete, the second arm will open and patients will receive CAR T cells reprogrammed to target both EGFR and CD19.

“We have made significant advances in CAR T-cell immunotherapy for hematologic malignancies, so much so that it is being incorporated into standard approaches for certain high-risk patients,” Albert told Cancer Network. She said there is still a long way to go when it comes to solid tumors in terms of refining the details. Albert also noted it will be a bit of time before there is an available product as a first-line therapy.

According to Albert, the bench-to-bedside pace has been swift overall, especially for the pediatric setting. “However, solid tumors are not at the same place and pose some unique challenges. CAR T cells have to find their way to bulk tumor sites throughout the body and overcome tumor microenvironment defenses.”

Albert said it is important that patients and their families are not given false hope. She noted that we are now in a time when significant advances are occurring in the lab and quickly leading to early-phase clinical trials. “Patients and researchers alike will always be anxious for new therapies to progress more quickly, and solid tumors may require even more innovation for success, but I would not call it false hope. The enthusiasm for CAR T-cell immunotherapy is legitimate,” she said.