Skip to content
Clinical Trials – home

Rare diseases

Investigational molecules

Locations

Our offerNewsroom

Not recruiting

Study of Tarlatamab alone or with FOLFIRI chemotherapy for patients with advanced digestive system or unknown origin neuroendocrine carcinomas

Verified siteRegistered drugNo placebo
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on advanced neuroendocrine carcinomas of the digestive system or unknown primary origin. The research evaluates two treatment approaches: tarlatamab (also known as AMG 757) used alone, or in combination with a chemotherapy regimen called FOLFIRI. FOLFIRI consists of three medications: irinotecan, fluorouracil, and folinic acid. Neuroendocrine carcinomas are rare tumors that develop from specialized hormone-producing cells in various organs of the digestive system.

The purpose of this research is to determine which treatment approach - either tarlatamab alone or combined with chemotherapy - is more effective in treating these cancers. The study will specifically look at patients whose tumors have already been treated with other therapies and have a certain protein marker called DLL3 on their cancer cells.

During the study, patients will receive their assigned treatment through intravenous infusion. The medications will be given according to a specific schedule, with regular monitoring of the patient's condition. The treatment period may continue for up to 36 months, depending on how well the treatment works and how well it is tolerated.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial Treatment Assignment

    You will be assigned to one of two treatment groups: either tarlatamab alone or tarlatamab with chemotherapy (FOLFIRI).

    Before starting treatment, your tumor tissue will be tested for DLL3 protein presence. Only patients with 1% or more DLL3-expressing cells can participate.

  2. Step 2

    Treatment Administration

    If assigned to tarlatamab alone: you will receive the medication through intravenous infusion.

    If assigned to combination treatment: you will receive tarlatamab plus FOLFIRI chemotherapy, which includes three medications:

    - Irinotecan through intravenous infusion

    - Folinic acid through intravenous injection

    - Fluorouracil through intravenous infusion

  3. Step 3

    Regular Health Monitoring

    Your health will be regularly monitored through:

    Blood tests to check organ function and blood cell counts

    Imaging scans to measure tumor response

    Quality of life assessments using a standardized questionnaire

    Regular checks for any side effects or health changes

  4. Step 4

    Treatment Duration

    Treatment will continue until one of these occurs:

    The disease shows progression

    Unacceptable side effects develop

    The study reaches its end date (estimated October 2029)

  5. Step 5

    Follow-up Period

    After completing treatment, you will need to avoid pregnancy or fathering a child for:

    60 days after the last dose of tarlatamab

    6 months after the last dose of FOLFIRI chemotherapy

    Your health status will continue to be monitored to assess long-term treatment outcomes

Who can join the trial?

18 criteria

  • Must be at least 18 years old
  • Must have confirmed neuroendocrine carcinomas (NECs) of the digestive system or unknown origin
  • Must provide written informed consent approved by the Ethics Committee
  • Must have adequate physical function with an ECOG score of 0-2 (scale measuring daily living abilities)
  • Must have disease that has spread or cannot be surgically removed, after previous treatment with either:
    • First-line platinum-based chemotherapy, or
    • First-line combination of immunotherapy and chemotherapy
    • Must have at least one measurable tumor
    • Must have tumors that test positive for DLL3 (specific protein marker) in at least 1% of cells
    • Must have adequate organ function, including:
      • Acceptable blood cell counts
      • Normal blood clotting function
      • Adequate liver function
      • Adequate kidney function
      • For women who can become pregnant:
        • Must have negative pregnancy test
        • Must use effective birth control during study and for 60 days after last dose
        • Must not be breastfeeding
        • For men with partners who can become pregnant:
          • Must use effective birth control during study and for 60 days after last dose
          • Must not donate sperm during study and for 60 days after last dose
          • Must not participate in other clinical trials during this study

Who cannot join the trial?

13 criteria

  • History of any neuroendocrine tumor (a type of tumor that starts in cells that produce hormones) other than digestive system or unknown origin
  • Previous treatment with tarlatamab or similar experimental medications
  • Active or untreated brain metastases (cancer that has spread to the brain)
  • Severe heart conditions including uncontrolled high blood pressure or recent heart attack
  • Active infections requiring systemic treatment (medications that affect the whole body)
  • Major surgery within 4 weeks before starting the study
  • Pregnant or breastfeeding women
  • Known allergies to study medications or their components
  • Participation in another clinical trial within 30 days before this study
  • Severe liver or kidney problems that could affect the study medication
  • Any condition that the study doctor believes would make participation unsafe
  • Unable to swallow medications or have conditions that would prevent proper absorption of the study drug
  • Mental conditions that would prevent understanding or following study instructions
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

  • Tarlatamab

    is an investigational medication being studied for treating neuroendocrine carcinomas of the digestive system or those with unknown origin. It is being tested both as a standalone treatment and in combination with other medications.

  • FOLFIRI

    is a combination chemotherapy regimen that includes multiple cancer-fighting drugs. It is commonly used to treat various types of cancer and in this study is being tested in combination with tarlatamab. FOLFIRI consists of the following medications: fluorouracil, leucovorin, and irinotecan. These medications work together to stop cancer cells from growing and dividing.

What is already known about the treatment

  • Tarlatamab

    A novel investigational therapeutic agent currently being studied in clinical trials for the treatment of advanced neuroendocrine carcinomas (NECs) of the digestive system or those of unknown primary origin. The medication is being evaluated both as a standalone treatment and in combination with FOLFIRI chemotherapy regimen, with the primary goal of preventing disease progression and improving overall survival rates. While the exact molecular mechanism is still under investigation in clinical trials, this targeted therapy represents a new approach in the treatment of aggressive neuroendocrine cancers, particularly focusing on cases affecting the digestive system.

  • FOLFIRI

    A combination chemotherapy regimen consisting of folinic acid, fluorouracil, and irinotecan, administered intravenously under medical supervision. This established treatment protocol is commonly used in various gastrointestinal cancers and is now being studied in combination with tarlatamab for treating advanced neuroendocrine carcinomas. The combination works by interfering with cancer cell DNA replication and division, effectively slowing or stopping tumor growth while potentially enhancing the therapeutic effects of tarlatamab.

Investigated diseases

  • Neuroendocrine Carcinoma (NEC) of the Digestive System

    A type of cancer that develops from specialized cells called neuroendocrine cells in the digestive tract. These cells have characteristics of both nerve cells and hormone-producing cells. The disease typically starts in the digestive system organs such as stomach, intestines, pancreas, or other parts of the gastrointestinal tract. NECs are fast-growing tumors that can spread to other parts of the body. The condition affects the body's ability to regulate various digestive functions and hormone production. These tumors can develop in different locations throughout the digestive system, leading to various symptoms depending on their location.

  • Neuroendocrine Carcinoma of Unknown Primary Origin

    A condition where neuroendocrine cancer cells are found in different parts of the body, but the original site where the cancer started cannot be identified. These tumors are discovered after they have already spread to other locations in the body. The disease maintains characteristics of neuroendocrine cells, producing hormones and other substances that can affect body functions. Despite the unknown origin, these tumors show similar behavior to other neuroendocrine carcinomas.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2024-514327-42-00Estimated enrolment87 patientsSponsorGrupo Espanol De Tumores Neuroendocrinos

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.