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

Study Summary

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.

Primary Outcome

The primary endpoint is safety, which will be measured by DLT using adverse events graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and ASTCT (CRS and ICANS). DLT will be defined as having 1) grade 3 - 5 non-hematologic adverse events (AEs) possibly, probably or definitely related to protocol treatment (radiation or combination of radiation and tarlatamab) by 8 weeks from start of radiation therapy; or 2) AEs possibly, probably, or definitely related to radiati

Conditions Studied

Interventions

• DRUG Tarlatamab
• RADIATION Concurrent Radiation Therapy
• RADIATION Sequential Radiation therapy

Study Locations (1)