Tarlatamab + Radiation for Cancer

(RABBIT Trial)

Overseen By Rachel E Jarrett, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: University of Arizona

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Charles Hsu, MD

Principal Investigator

University of Arizona

Ricklie Julian, MD

Principal Investigator

University of Arizona

Eligibility Criteria

This trial is for patients with various cancers, including lung, skin, and bladder cancer. Participants must have tumors expressing DLL3 and be suitable for radiation therapy. Specific eligibility criteria are not provided but typically include factors like age, health status, and prior treatments.

Inclusion Criteria

Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures

I am 18 years old or older.

Minimum life expectancy of 12 weeks

Exclusion Criteria

I have not received any vaccines during the study period.

I don't have allergies to the study drugs and can attend all study visits.

I am not planning to conceive, and will follow the study's birth control requirements.

Treatment Details

Interventions

• Concurrent Radiation Therapy (Radiation)
• Sequential Radiation therapy (Radiation)
• Tarlatamab (Bi-specific T-Cell Engager)

Trial Overview The study tests Tarlatamab combined with standard radiation therapy (RT), either given at the same time or sequentially. It starts with extracranial sites and may expand to cranial sites if safe. The goal is to assess safety first then efficacy, especially in non-small cell lung cancer types.

Participant Groups

Group I: Tarlatamab Monotherapy Cohort Experimental Treatment 1 Intervention

If the sequential safety endpoint is not met, then the study will proceed to another de-escalation phase, where 10 patients will receive tarlatamab alone.

Group II: Sequential radiation therapy cohort Experimental Treatment 2 Interventions

If the concurrent main cohort safety endpoint is not met, then the study will proceed to de-escalation, where 20 patients will be enrolled on the sequential radiation therapy cohort. In this cohort patients will receive sequential tarlatamab and RT to cranial and extracranial RT sites. Standard of care RT 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/ICANS.

Group III: Concurrent Main Cohort Experimental Treatment 2 Interventions

Patients enrolled to this cohort will receive tarlatamab with concurrent radiation therapy (RT) to extracranial sites (n=20-24 extracranial RT with a minimum of 10 thoracic patients). Patients will receive tarlatamab at a step-up dose of 1 mg on Cycle 1 Day 1 and then 10 mg on cycle 1 Day 8 and Cycle 1 Day 15 and every 2 weeks thereafter (on days 1 and 15 of each cycle) until radiographic progression or disease progression or 24 months, whichever is earlier. Patients will receive concurrent RT to extracranial sites as per standard of care starting as early as Cycle 1 Day 16 and as late as Cycle 2 Day 28, assuming there is no ongoing cytokine release syndrome (CRS) or immune-effector cell-associated neurotoxicity Syndrome (ICANS).

Group IV: Concurrent Cranial Cohort Experimental Treatment 2 Interventions

If the safety endpoint in the Concurrent Main Cohort is met, enrollment will expand to the Concurrent Cranial Cohort. 6-10 patients will receive tarlatamab with concurrent radiation therapy to cranial sites as described in the Concurrent Main Cohort.

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London