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

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.

Conditions

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

Interventions

DRUG

Tarlatamab

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.

RADIATION

Concurrent 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).

RADIATION

Sequential 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).

Sponsors & Collaborators

• Amgen

  collaborator INDUSTRY

• University of Arizona

  lead OTHER

Principal Investigators

• Charles Hsu, MD · University of Arizona

• Ricklie Julian, MD · University of Arizona

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-08

Primary Completion

2030-05-31

Completion

2030-05-31

FDA Drug

Yes

Countries

• United States

Study Locations