Trials / Recruiting

RecruitingNCT06814496

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

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 30 (estimated)

Sponsor: University of Arizona · Academic / Other
Sex: All
Age: 18 Years – 99 Years
Healthy volunteers: Not accepted

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.

Detailed description

This is a Phase I, Open label, Single Arm, Multi-center Study, with nested Phase II to examine safety of standard palliative and consolidative RT regimens in a main cohort of patients with tumor histologies with high prevalence of DLL3 (N=20-24) with an extracranial site (primary or metastatic) amenable to radiation (not allowing for re-irradiation of the same lesion, with a minimum of 10 thoracic sites. Given the potential toxicity of ICANS with tarlatamab, once deemed safe in the main cohort, we will allow for expansion for treatment of cranial sites amenable to radiation (excluding lesion re-irradiation except for stereotactic radiosurgery / fractionated stereotactic radiosurgery \[SRS/fSRS\] after prior whole brain RT or prophylactic cranial irradiation \[PCI\]) with continued enrollment in the main cohort. Given the need to determine safety of administration of tarlatamb with RT, if safety is not met for concurrent administration in the main cohort, we would discontinue concurrent treatment, and assess safety in a sequential RT and tarlatamab cohort, as temporal de-escalation. If safety is not met in the sequential cohort, treatment with RT will be discontinued and enrollment will continue with tarlatamab monotherapy, not requiring patients having a site amenable to RT and enriching for patients without SCLC. In the nested phase II, we will assess efficacy of radiation and tarlatamab amongst patients with tumors with high prevalence of DLL3 or those who have positive DLL3 (≥1% per IHC), including but not exclusive to SCLC. This would allow for potential evaluation of safety and response for tumors beyond the DeLLPhi 300/301 studies. The study population will include patients ≥18 years of age with primary/metastatic sites amenable to external beam radiation treatment refractory solid tumors of: 1. small cell histology 2. high grade / poorly differentiated neuroendocrine histology 3. tumor histologies with high prevalence of DLL3 (≥ 50% prevalence), including but not limited to: melanoma, medullary thyroid cancer, sinonasal undifferentiated carcinoma, esthesioneuroblastoma, bladder cancer, testicular cancer, glioblastoma multiforme, cervical cancer; large cell neuroendocrine tumor of lung, non-small cell lung cancers with mixed neuroendocrine features, and Merkel cell carcinoma OR 4. Patients with DLL3+ tumors (≥1% IHC) Up to 30 patients will be enrolled.

Conditions

Interventions

Type	Name	Description
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).

Timeline

Start date: 2025-09-08
Primary completion: 2030-05-01
Completion: 2030-05-01
First posted: 2025-02-07
Last updated: 2025-10-09

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06814496. Inclusion in this directory is not an endorsement.