Actively Recruiting

Phase 1
Phase 2
Age: 18Years - 99Years
All Genders
NCT06814496

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

Led by University of Arizona · Updated on 2026-04-28

30

Participants Needed

2

Research Sites

242 weeks

Total Duration

On this page

Sponsors

U

University of Arizona

Lead Sponsor

A

Amgen

Collaborating Sponsor

AI-Summary

What this Trial Is About

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

Official Title

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

Who Can Participate

Age: 18Years - 99Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Provided informed consent before any study procedures
  • 18 years of age or older at consent
  • Confirmed relapsed or refractory small cell lung cancer, other small cell histology tumors, high grade neuroendocrine tumors with high DLL3 prevalence, or DLL3-positive tumors
  • Disease progressed or recurred after at least one prior therapy and is treatment refractory
  • Willing to provide archived tumor tissue or undergo pretreatment biopsy if needed
  • ECOG performance status between 0 and 2
  • Minimum life expectancy of 12 weeks
  • Prior or concurrent malignancies that will not interfere with study assessments
  • Measurable lesions per RECIST 1.1 within 28 days before first tarlatamab dose
  • Eligible for external beam radiation to a previously unirradiated measurable lesion
  • For extracranial RT cohort, minimum 10 subjects with thoracic lesions
  • Treated brain metastases allowed if stable and meeting specific criteria
  • For cranial RT cohort, untreated brain lesions or previously irradiated brain lesions meeting criteria allowed
  • Adequate organ function including hematological, coagulation, renal, hepatic, pulmonary, and cardiac function
Not Eligible

You will not qualify if you...

  • Re-irradiation of same lesion unless specified exceptions
  • No lesions amenable to radiation therapy (except in tarlatamab monotherapy cohort)
  • Planned re-irradiation of previously irradiated sites
  • Leptomeningeal disease needing craniospinal irradiation
  • Evidence of interstitial lung disease or active non-infectious pneumonitis
  • History of recurrent pneumonitis grade 2 or higher or severe immune-related adverse events
  • Unresolved toxicity from prior anti-tumor therapy above grade 1 except stable alopecia or irreversible toxicities
  • Recent myocardial infarction or symptomatic congestive heart failure within 12 months
  • History of recent arterial thrombosis within 12 months
  • Active uncontrolled infection within 7 days before first tarlatamab dose
  • History of hypophysitis or pituitary dysfunction
  • Positive tests indicating active hepatitis B or C infection
  • Major surgery requiring hospitalization over 3 days within 28 days before first dose
  • Active autoimmune disease needing systemic treatment within past 2 years
  • HIV infection except well-controlled cases with monitoring
  • Prior treatment with tarlatamab
  • Anti-cancer therapy within 30 days before first dose except certain chemotherapy with resolved toxicity
  • Immunodeficiency or immunosuppressive therapy within 7 days before first dose
  • Use of live or live-attenuated vaccines within 28 days before first dose and during treatment
  • Female subjects unwilling to use contraception or breastfeeding or pregnant
  • Male subjects unwilling to use contraception or abstain from sperm donation during and after treatment
  • Known sensitivity to study treatments
  • Likely inability to complete study procedures
  • Other significant medical conditions posing safety risk or interfering with study completion

AI-Screening

AI-Powered Screening

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Trial Site Locations

Total: 2 locations

1

Arizona Cancer Center at UMC North/University Medical Center

Tucson, Arizona, United States, 85719

Actively Recruiting

2

University of Washington Fred Hutchinson Cancer Center

Seattle, Washington, United States, 98109

Not Yet Recruiting

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Research Team

R

Rachel E Jarrett, MPH

CONTACT

M

Michele Chu, MS

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

4

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