Dr Schlechter on TAC01-HER2 Therapy in HER2+ Solid Tumors

Benjamin L. Schlechter, MD, senior physician, Dana-Farber Cancer Institute, instructor, medicine, Harvard Medical School, discusses the future implications of TAC01-HER2 therapy in patients with HER2-positive solid tumors.

The ongoing, phase 1/2 TACTIC-2 trial (NCT04727151) is evaluating the efficacy and safety of autologous TAC01-HER2 T-cell therapy in patients with HER2-positive breast, colorectal, gall bladder, gastroesophageal junction (GEJ), gastric, esophageal, lung, and ovarian cancers.

Interim findings from this trial, which were presented at the 2023 ASCO Annual Meeting, showed 2 partial responses with the therapy, 1 in a patient with refractory GEJ cancer, and 1 in a patient with refractory gastric cancer. In the patients with gastric, GEJ, or esophageal cancer, the disease control rate (DCR) was 83% and the overall response rate was 33%. In heavily pretreated patients, the DCR was 67%. One dose-limiting toxicity (DLT), grade 3 pneumonitis, was observed, and 1 patient had grade 3 cytokine release syndrome. No incidence of immune effector cell–associated neurotoxicity syndrome has been reported.

These findings indicate that HER2 can be targeted safely and effectively in several solid tumor populations, Schlechter says. The differences in responses between the heavily pretreated breast cancer population and the gastrointestinal (GI) cancers population may have arisen because of the biology of each disease, Schlechter explains. The patients with breast cancer were pretreated with chemotherapy and HER2-directed therapies, which bind differently to TAC01-HER2 and create a tumor microenvironment that may suppress immune responses to this therapy, Schlechter notes. However, the patients with GI cancer were less heavily pretreated and therefore may have had a more favorable tumor microenvironment for TAC01-HER2, according to Schlechter. In addition, heavily pretreated patients have inferior T cells, which may produce inferior outcomes when generated as effector T-cell therapies, Schlechter says. Delivering TAC01-HER2 as an earlier line of therapy may produce optimal patient outcomes, Schlechter notes.

Moreover, these findings demonstrate that TAC01-HER2, a non-CAR T-cell therapy, can safely target HER2, which is expressed on both tumor and normal tissue, Schlechter emphasizes. Although other HER2-directed therapies can produce excessive toxicities, TAC01-HER2 does not cause as many off-target effects and lowers the risk for DLTs, Schlechter says. A T-cell therapy that is slightly less effective than conventional treatment options but produces fewer DLTs is a favorable alternative compared with a drug that may become unusable in many patients because of its toxicity profile, Schlechter concludes.