RecruitingPhase 1Phase 2NCT06814496

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

RAdiation comBined With BIspecific T-Cell Engager in DLL3 Expressing Tumors (RABBIT) Study: A Phase I/II Study of AMG757 / Tarlatamab and Concurrent Radiation Therapy in Tumors With High Prevalence of DLL3

Sponsor

University of Arizona

Enrollment

30 participants

Start Date

Sep 8, 2025

Study Type

INTERVENTIONAL

Conditions

Cervical Cancer Melanoma Bladder Cancer Testicular Cancer Large Cell Neuroendocrine Carcinoma of the Lung Glioblastoma Multiforme Medullary Thyroid Cancer Sinonasal Undifferentiated Carcinoma Esthesioneuroblastoma

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.

Eligibility

Min Age: 18 YearsMax Age: 99 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether combining radiation therapy with a bispecific antibody drug (a drug that links immune cells directly to cancer cells) works better for cancers that express a protein called DLL3. DLL3 is found on certain aggressive tumor types, including small cell lung cancer and some neuroendocrine tumors. The goal is to see if this combination can boost the immune system's ability to attack the cancer. **You may be eligible if...** - You are 18 or older - You have a confirmed relapsed or treatment-resistant cancer that expresses DLL3, including: small cell lung cancer, other small-cell or neuroendocrine tumors, or certain other tumor types with confirmed DLL3 positivity - Your cancer has come back or is not responding to prior treatments **You may NOT be eligible if...** - Your tumor does not test positive for DLL3 - You have certain serious infections or organ function problems - You cannot tolerate radiation therapy Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGTarlatamab

Tarlatamab will be administered at a step-up dose of 1mg on Cycle 1 Day 1 and then 10 mg on Cycle 1 Day 8 and Cycle 1 Day 15 and every 2 weeks thereafter. For cycle 2 onwards, tarlatamab infusion will occur every 2 weeks on days 1 and 15 of each cycle.

RADIATIONConcurrent Radiation Therapy

Standard of care RT can begin as early as Cycle 1 Day 16 and as late as Cycle 2 Day 28, assuming there is no ongoing CRS (extracranial)/ICANS (cranial).

RADIATIONSequential Radiation therapy

Standard of care radiation therapy can occur prior to Cycle 1 Day 1 (if radiation treatment is completed \<7 days prior to the start of tarlatamab) or be interdigitated with tarlatamab with a 7-day washout between RT and infusion, with RT to begin as early as Cycle 1 Day 22 and as late as cycle 2 Day 28, assuming no ongoing CRS (extracranial)/ICANS (cranial).