Dr. Tiwari on Ongoing Research in HER2+/HER2-Low Breast Cancer

Shruti Tiwari, MD, medical oncologist, Virginia Cancer Specialists, discusses efforts to address unmet needs and unanswered questions through ongoing research in HER2-positive and HER2-low breast cancer.

Efforts to develop novel agents and more effective treatment regimens within the landscape of HER2-positive and HER2-low breast cancer are constantly evolving, Tiwari begins. Clinical trials play a pivotal role in this dynamic paradigm, with a myriad of new trials and innovative therapies that have the potential to transform disease management in this space, she emphasizes.

Researchers at Virginia Cancer Specialists are actively engaged in 2 clinical trials focused on HER2-low cancers and antibody-drug conjugates (ADCs), Tiwari introduces. One trial is evaluating BNT323/DB-1303, a novel HER2-directed ADC with a TROP1/2 payload, she states. Data previously reported from a first-in-human, multicenter phase 1/2 study (NCT05150691) showed that DB-1303 was well tolerated and produced preliminary antitumor activity in heavily pretreated patients with advanced/metastatic solid tumors, particularly those with HER2-positive breast cancer and brain metastasis as well as in HER2-low disease. This agent is comparable to prior ADCs, but is notable for its tolerability and reduced incidence of alopecia compared to previous ADCs, Tiwari adds.

Despite the successes of current treatments, challenges remain, particularly in terms of treatment durability and tolerability, Tiwari continues. For patients experiencing disease progression after receiving highly effective ADCs such as fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), there is a critical need for alternative therapies, she explains. Accordingly, a second trial at Virginia Cancer Specialists is exploring the use of a novel immune-stimulating ADC to combat disease progression following treatment with T-DXd, Tiwari details. These clinical trials aim to provide new therapeutic approaches that can address treatment gaps and overcome resistance.

The significance of these trials is reflected in the willingness of patients to travel to Virginia where the trials are being run, seeking access to cutting-edge therapies that are not widely available, Tiwari notes. By participating in these trials, researchers can advance care and provide patients with more effective and better-tolerated treatment options, Tiwari concludes.