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Trial to assess CAR T-cell therapy for HER2-positive metastatic breast cancer
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Researchers at City of Hope have opened a first-in-human clinical trial to assess the use of chimeric antigen receptor T-cell therapy for patients with HER2-positive breast cancer that spread to the brain.
Patient accrual is underway.
“For a woman who already has breast cancer, learning that a brain tumor has developed can be a frightening diagnosis because there are few treatment options available. CAR T-cell therapy may be another tool in our fight against this devastating disease,” Jana Portnow, MD, associate professor in the department of medical oncology and therapeutics research, and associate director of the brain tumor program at City of Hope, said in a press release.
HemOnc Today spoke with Saul Priceman, PhD, assistant professor in the CAR T-cell immunotherapy program at City of Hope, about the rationale for CAR T-cell therapy for this patient population, how the trial will be conducted, the timeline for results and the potential need this treatment modality could meet.
Question: How did this program come about?
Answer: HER2 is a well-validated target and multiple effective therapies have been developed for patients with breast cancer. We performed extensive preclinical testing and found that targeting HER2 with CAR T cells was highly efficacious for treating brain metastatic breast cancer in animal models. Also, we at City of Hope have been treating patients with glioblastoma with CAR T cells administered directly into the central nervous system by intraventricular delivery rather than intravenously, and we believed that this route of delivery would more effectively target brain metastatic breast cancer. City of Hope also was the first to treat patients with glioblastoma with CAR T cells by intraventricular route of delivery to reach distant sites of disease. Based on this experience, we embarked on our clinical program utilizing HER2 CAR T cells for the treatment of patients with breast cancer brain metastases.
Q: What is the rationale for using CAR T-cell therapy with this patient population?
A: Early-stage HER2-positive breast cancer is highly treatable. However, when tumors reach the brain — up to 50% of patients who have HER2-positive breast cancer will ultimately develop brain metastases — there are limited treatment options, in part due to the blood-brain barrier. Overall, these patients have a poor survival of about 12 months from the time of diagnosis of brain metastasis. For us, it was a ‘no-brainer’ to extend our CAR T-cell research to this patient population.
Q: How will you conduct the trial?
A: Patients with HER2-positive breast cancer who have brain and/or leptomeningeal metastases will be eligible for this dose-escalation phase 1 study. After we collect the patient’s T cells to manufacture the HER2 CAR T-cell product, he or she will undergo placement of a catheter into the cerebral ventricles. We will administer the HER2 CAR T cells intraventricularly weekly for 3 weeks and then assess patient safety and response to therapy.
Q: What is the timeline for results?
A: We anticipate it will take approximately 2 years to complete the study.
Q: What is the potential need that this treatment modality could meet if it is proven safe and effective?
A: All too often women with HER2-positive metastatic breast cancer well-controlled with HER2-targeted systemic therapies ultimately die of their brain metastatic disease. These patients do not have any durable therapeutic options for their CNS disease. We hope that by administering our HER2-targeting CAR T cells directly into the CNS, we can improve survival of these patients.
Q: Is there anything else that you would like to mention?
A: A: HER2 is overexpressed most frequently in patients with breast cancer, but it also can be overexpressed in other solid tumors, such as gastric and ovarian cancers. Although we anticipate that most of the patients who enroll in this HER2 CAR T-cell study will have breast cancer, the study’s eligibility criteria allow any HER2-positive patient who has brain metastases to participate. Moreover, HER2 is not the only target for which we are developing CAR T-cell therapies at City of Hope. We anticipate in the future that breast cancer as well as other solid tumors will be managed effectively with CAR T-cell immunotherapy. – by Jennifer Southall
For more information:
Saul Priceman, PhD, can be reached at City of Hope, 1500 E. Duarte Road, Duarte, CA, 91010.
Disclosure: Priceman reports no relevant financial disclosures.