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Trial to assess CAR T-cell therapy for relapsed, refractory solid tumors
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A trial underway at Seattle Children’s Hospital will evaluate chimeric antigen receptor T-cell therapy for children and young adults with relapsed or refractory noncentral nervous system EGFR-expressing solid tumors.
The EGFR protein often is expressed in childhood sarcoma, kidney tumors and neuroblastoma; however, the phase 1 STRIvE-01 trial will not be limited to patients with these malignancies.
Researchers plan to enroll up to 36 children and young adults across two arms to assess the dosing, safety and tolerability of CAR T-cell therapy. Results could inform the development of future CAR T-cell trials, as well as identify the most effective targets and therapeutic combinations for pediatric solid tumors.
“Despite employing modern treatments that offer more intensive therapy or new drug combinations for children with solid tumors, we have been unable to improve outcomes for our highest-risk patient groups,” Katie Albert, MD, assistant professor in the department of hematology and oncology at Seattle Children’s Hospital, said in a press release. “It is those groups that push us to come up with innovative approaches so that we can see all of our patients cured of their cancer.”
HemOnc Today spoke with Albert about the trial, why the approach may be successful, and the anticipated timeline for completion.
Question: How did this trial come about?
Answer: This study is our first ‘basket’ solid tumor CAR T-cell protocol. It is open to all relapsed or refractory solid tumors that meet eligibility and express the target EGFR. There has been a lot of success using T cells to specifically target CD19 in B-cell lymphoblastic malignancies. Naturally, the focus has shifted to other malignancies, including brain tumors and solid tumors.
Q: Why might this approach be successful?
A: EGFR is expressed by many types of solid tumors among both children and adults, and it has been a focus of anticancer therapy for quite some time. Because EGFR also is expressed in normal tissue, it has been difficult to treat patients with EGFR-targeted therapy without having significant toxicity to the normal tissues that express EGFR. Our CAR T cells are generated from an EGFR antibody that is specific for the EGFR protein expressed by tumors and, in clinical trials, generally has caused minimal toxicity to other EGFR-expressed tissues.
Q: How will you conduct the trial?
A: All patients will be treated at Seattle Children’s Hospital. The trial is open to patients aged 1 to 26 years. However, the first two patients on each arm have to be aged 15 or older for safety purposes. Any patient from the United States can inquire about the study if they meet eligibility criteria, and the trial eventually will be open to international patients. Tumors will be screened for EGFR expression via immunohistochemical staining. If the screen is positive, the patient will come to Seattle Children’s Hospital to be evaluated. He or she will undergo apheresis and return a few weeks later once their CAR T cells have been generated. For the first arm of the study, we will administer CAR T cells directed at only at EGFR. The second arm of the study uses two targets, EGFR and CD19. We hope that, by using a second target found on cells that are abundant throughout circulation, B lymphocytes will enhance expansion and persistence of the CAR T cells, making them more effective at trafficking to the sites of bulk tumor and eliminating tumor cells.
Q: What is the timeline for results?
A: We project we will enroll 30 to 36 patients to meet our trial goals, and that will take about 3 years.
Q: What are the next steps?
A: If this approach is safe and feasible, we will look at whether we observe efficacy with any of the tumor types. We then would move on to a phase 2 trial in which we would specifically treat those diagnoses with the dose established in the phase 1 trial. Our hope is that the treatment will be effective against one or more tumor types so that we can employ it for patients with relapsed or refractory disease, and potentially use it in certain patient populations as part of their upfront treatment.
Q: Is there anything else that you would like to mention?
A: There is great diversity in tumor antigen targets in solid tumors, and we plan to use other targets in several other trials. We have put a lot of thought into considering innovative approaches for CAR T-cell therapy in solid tumors, as some of the obstacles are quite different from hematologic malignancies. We have to ensure that CAR T cells are able to travel to the bulk tumor sites, survive the tumor microenvironment and persist for a long time so that they will be effective in both the short term and long term. – by Jennifer Southall
For more information:
Katie Albert, MD, can be reached at Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105; email: katie.albert@seattlechildrens.org.
Disclosure: Albert reports no relevant financial disclosures.