Actively Recruiting
Radiation Combined With Bispecific T-Cell Engager Tarlatamab in DLL3 Expressing Tumors A Phase I/II Study Evaluating Safety and Response with Concurrent Radiation Therapy
Led by University of Arizona · Updated on 2026-05-20
30
Participants Needed
2
Research Sites
N/A
Total Duration
On this page
Sponsors
U
University of Arizona
Lead Sponsor
A
Amgen
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of combining the drug tarlatamab with radiation therapy (RT) in patients with various tumors that have high levels of DLL3, a protein found in some cancers. This Phase I/II study focuses on patients aged 18 and older who have tumors suitable for radiation, including small cell lung cancer and other neuroendocrine tumors, as well as several other cancer types. The study aims to understand the safety of giving tarlatamab together with radiation and to assess tumor responses in these patients. Participants are divided into groups based on how they receive tarlatamab and radiation. One group receives tarlatamab with concurrent radiation to extracranial sites, starting with small doses of tarlatamab that increase over time and radiation beginning between Cycle 1 Day 16 and Cycle 2 Day 28 if no severe side effects occur. If this is safe, another group will receive the same treatment but with radiation to brain sites. If not safe, patients will receive radiation and tarlatamab sequentially, with a gap between treatments, or tarlatamab alone if radiation is unsafe. Tarlatamab is given every two weeks during treatment cycles for up to 24 months or until disease progression. During the study, participants undergo regular assessments including scans to monitor tumor responses and side effects. The main outcome measured is the percentage of patients who experience significant toxicities related to treatment over up to 24 months. Secondary outcomes include tumor response rates, overall survival, progression-free survival, and treatment safety in different patient groups. Researchers also monitor for specific side effects like cytokine release syndrome and neurotoxicity. The study includes follow-up visits and ongoing safety checks throughout treatment.
CONDITIONS
Brief Title
Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors
Who Can Participate
Eligibility Criteria
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 or other small cell histology tumors
- Tumors with high DLL3 prevalence (≥50%) or DLL3 positive (≥1% by IHC)
- Progressed or recurred after at least one line of therapy and treatment refractory
- Willing to provide archived tumor tissue or undergo pretreatment biopsy
- ECOG performance status of 0 to 2
- Life expectancy of at least 12 weeks
- Prior or concurrent malignancies allowed if they do not interfere with study
- Measurable lesions per RECIST 1.1 within 28 days before first dose
- Eligible for external beam radiation to a previously unirradiated, measurable lesion
- Specific criteria for extracranial and cranial radiation sites
- Adequate organ function including hematologic, coagulation, renal, hepatic, pulmonary, and cardiac function
You will not qualify if you...
- Re-irradiation unless allowed as per specific criteria
- No lesions amenable to radiation (except for monotherapy cohort)
- Planned re-irradiation of previously irradiated site
- Leptomeningeal disease requiring craniospinal irradiation
- Interstitial lung disease or active non-infectious pneumonitis
- History of recurrent pneumonitis grade 2 or higher or severe immune reactions
- Unresolved toxicity from prior therapy above grade 1 except alopecia or stable irreversible toxicities
- Recent myocardial infarction or symptomatic heart failure within 12 months
- Recent arterial thrombosis within 12 months
- Active uncontrolled infection within 7 days prior to first dose
- History of hypophysitis or pituitary dysfunction
- Active hepatitis B or C infection
- Major surgery with hospitalization over 3 days within 28 days prior
- Active autoimmune disease requiring systemic treatment in past 2 years
- HIV infection except controlled cases with monitoring
- Prior therapy with tarlatamab
- Recent anti-cancer therapy within 30 days with exceptions
- Immunodeficiency or immunosuppressive therapy within 7 days prior
- Use of live vaccines within 28 days before and during study treatment
- Female or male unwilling to use contraception or abstinence during and 60 days after treatment
- Breastfeeding or planning pregnancy during and 60 days after treatment
- Sensitivity to study products
- Unlikely to comply with study visits or procedures
- Other clinically significant disorders posing risk or interfering with study
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 24 months or until radiographic or disease progression, whichever is earlier
Participants receive tarlatamab drug infusions and radiation therapy according to their assigned cohort, either concurrently or sequentially. Tarlatamab is given at a step-up dosing schedule starting at Cycle 1 Day 1 and continues every 2 weeks. Radiation therapy timing depends on cohort assignment and safety evaluations.
Infusions every 2 weeks starting Cycle 1 Day 1; radiation therapy starts between Cycle 1 Day 16 and Cycle 2 Day 28 depending on cohort and safety
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
Actively Recruiting
Research Team
R
Rachel E Jarrett, MPH
M
Michele Chu, MS
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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