Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors

Phase I study to examine safety of the addition of concurrent tarlatamab with standard palliative and consolidative RT regimens , with a main cohort of N=20-24 patients with extracranial anatomic radiation sites. I) After lead in of 10 patients demonstrating safety of treatment, allow for expansion to cranial sites of disease (N=6-10) with continued enrollment in main cohort II) If toxicity criteria is not met in concurrent RT tarlatamab cohort, we will continue with sequential RT, either A) delivered within 7 days prior to cycle 1 day 1, or B) delivered during cycle 1 -2 but with pre- and post-RT washout of 7 days with no drug during RT, to examine safety in a temporally spaced setting. III) If sequential tarlatamab and radiation is not deemed safe, we would allow for continued enrollment to assess efficacy of drug sans radiation treatment, enriching for tumors not of small cell lung cancer histology and allowing for patients without sites amenable to RT. A nested phase II study will attempt to assess for ORR and safety of study intervention amongst tumors not of small cell lung cancer histology.

NCT Number	NCT06814496
Lead Sponsor	University of Arizona Collaborators: Amgen
Conditions	Melanoma, Medullary Thyroid Cancer, Sinonasal Undifferentiated Carcinoma, Esthesioneuroblastoma, Bladder Cancer, Testicular Cancer, Glioblastoma Multiforme, Cervical Cancer +3 more
Enrollment	30 participants
Start Date	2025-09-08
Primary Completion	2030-05 (estimated)
Study Completion	2030-05 (estimated)
Updated on ClinicalTrials.gov	2026-07-20