Two Complete Responses with HER2-Targeted CAR T-Cell Immunotherapy in Sarcoma Treatment!

At the American Association for Cancer Research (AARC) 2019 Congress held in Atlanta, United States, in April 2019, early results from several highly noteworthy studies were presented. One involved a disease with very limited treatment options among rare cancers, namely soft tissue sarcomas , and their treatment with a form of cellular immunotherapy , CAR T, with results from a phase-1 clinical trial.

In the video below, you can see how the living cancer drug, CAR-T cell therapy, is prepared and administered (Turkish subtitles can be selected).

According to these clinical trial results, chemotherapy combined with chimeric antigen receptor (CAR) T cells targeting the HER2 protein was both effective and safe in children and adults with HER2-positive sarcoma.

Children and adults with recurrent or treatment-resistant sarcoma have limited treatment options. Curative salvage regimens exist for certain types of sarcoma, but their chances of success are low and the treatments may have considerable side effects.

The HER2 receptor, involved in cell growth and proliferation, may be positive in up to %40 of osteosarcomas (bone cancer), a common sarcoma type. The percentage of other sarcoma types that are HER2-positive is unknown. HER2 positivity is associated with more aggressive tumor biology, and earlier studies showed that HER2-targeted treatments are effective in HER2-positive sarcomas.

One of the young researchers, Dr. Shoba Navai of Baylor College of Medicine in Houston, United States, says: “Experimental studies by our group suggested that HER2-directed CAR T cells might have activity in patients with sarcoma even when anti-HER2 antibody drugs do not.”

In this study, previously treated patients with advanced sarcoma received three doses of HER2-directed CAR T-cell immunotherapy after low-dose chemotherapy that suppresses bone marrow (fludarabine with or without cyclophosphamide). Responders received five additional CAR T-cell treatments without chemotherapy.

Results

• The data reported by Dr. Navai are based on patients aged 4 to 54, with 10 patients in total; they had treatment-resistant, metastatic HER2-positive sarcoma (5 osteosarcomas, 3 rhabdomyosarcomas, and 1 with Ewing sarcoma and synovial sarcoma).
• Continued proliferation of the modified CAR T cells after infusion into the body was documented in all but two patients. Median peak cell expansion occurred on day 7, and CAR T cells were detected in all patients 6 weeks after administration.
• Two patients had a complete response (disappearance of all signs of disease), four had stable disease, and four had progressive disease.
• Side effects were mild, and opportunistic infection, lung or heart toxicity and neurotoxicity were not observed.

Comment

This research is a small phase I trial with impressive and promising results in a disease such as sarcoma, for which options are limited. Therefore, CAR T-cell immunotherapies will rapidly begin to be tested in larger patient groups with solid (solid/organ) cancers. Important developments in the use of CAR T-cell immunotherapy for organ cancers