Dr. Pothuri Discusses Emerging ADCs in HER2-Expressing Endometrial Cancer

In an interview during 2026 SGO Annual Meeting, Bhavana Pothuri, MD, professor at NYU Grossman School of Medicine and director of Gynecologic Oncology Research at NYU Langone Health and the Perlmutter Cancer Center, shared encouraging early efficacy and safety findings from a global phase 2 study (NCT05150691) evaluating trastuzumab pamirtecan (DB-1303/BNT323) in patients with previously treated HER2-expressing advanced or metastatic endometrial cancer.

Trastuzumab pamirtecan is a novel HER2-directed antibody-drug conjugate (ADC) designed to deliver a cytotoxic payload directly to HER2-expressing tumor cells, enabling targeted tumor killing while limiting off-target effects. In a heavily pretreated patient population with limited remaining treatment options, the agent demonstrated a strong signal of antitumor activity, with an objective response rate approaching 50%. Dr. Pothuri emphasized that this level of response is particularly notable given the refractory nature of the disease and the limited efficacy of currently available therapies in this setting.

Durability of response was also highlighted as an important finding. The median duration of response was reported at 9.9 months, suggesting that many patients not only responded to therapy but also maintained disease control for a clinically meaningful period of time. Together, these results support trastuzumab pamirtecan as a potential new treatment option capable of both inducing tumor shrinkage and sustaining benefit over time.

Safety considerations remain an important focus for ADC-based therapies. Overall, trastuzumab pamirtecan was described as generally well tolerated, though careful monitoring for interstitial lung disease (ILD) is essential. Early detection and prompt management of ILD are critical to minimizing the risk of more severe complications and ensuring safe delivery of therapy.

Pothuri also discussed related findings with Sofetabart mipitecan, noting its activity as an α-targeting ADC with a payload designed to enhance antitumor efficacy. Across a cohort of more than 100 patients, the overall response rate was approximately 50%, with activity observed even in ultra-low HER2 expressors, where responses reached 40%. Importantly, clinical activity was also seen in patients previously treated with mirvetuximab soravtansine, including an objective response rate of 61% among those previously exposed, suggesting that efficacy may persist even after prior ADC therapy.

Taken together, these findings underscore the growing potential of HER2-targeted and α-directed ADC strategies in endometrial cancer, particularly in heavily pretreated populations where treatment options remain limited. Continued study will be essential to better define long-term outcomes, optimize sequencing, and further refine safety management strategies.