Tarlatamab

Dr. Himisha Beltran discussed DLL3 as a therapeutic target for neuroendocrine prostate cancer at the 2024 ESMO Congress. DLL3 expression increases in castrate-resistant prostate cancer and is crucial for maintaining a neuroendocrine phenotype. Despite early promising results with DLL3-targeted therapies like Rova-T, efficacy was limited and toxicity high. Ongoing DLL3-targeted therapies include T cell engagers, ADCs, radionuclides, and CAR-T. Tarlatamab, a DLL3-targeted bi-specific T cell engager, showed limited efficacy in neuroendocrine prostate cancer. MK-6070, another DLL3-targeted T cell engager, demonstrated strong anti-tumor activity in neuroendocrine prostate cancer models. Future PET imaging with ⁸⁹Zr-SC16 may aid in patient selection and resistance pattern understanding.

Sally Lau, MD, discusses her role in the DeLLphi-304 trial, focusing on the accelerated approval of Imdelltra for relapsed small-cell lung cancer. She highlights the importance of nurse navigators and diversity grants in supporting patient enrollment and retention in trials, emphasizing the need for early involvement and responsive sponsors. Lau's passion for clinical trials stems from witnessing direct patient benefits and innovative treatment approaches.

Ifinatamab deruxtecan (I-DXd) showed improved efficacy in heavily pretreated extensive-stage small cell lung cancer (ES-SCLC) patients, with a 12-mg/kg dose achieving a 54.8% overall response rate (ORR) vs 26.1% for an 8-mg/kg dose. The 12-mg/kg dose also had a 90.5% disease control rate (DCR) and a median duration of response (DOR) of 4.2 months, compared to 7.9 months for the 8-mg/kg dose. Both doses were generally well-tolerated, with gastrointestinal and hematologic toxicities as the primary adverse effects.