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

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What is this study about?

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.

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 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 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 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 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 Study?

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 Study?

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

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut De Cancerologie De Lorraine	Vandoeuvre Les Nancy	France
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France
Oncopole Claudius Regaud	Toulouse	France
Hospital Universitario Y Politecnico La Fe	Valencia	Spain
Institut Gustave Roussy	Villejuif	France

Other Sites

Site Name	City	Country
Centre Antoine Lacassagne	Nice	France
Hospital Edouard Herriot	Lyon	France
Universidade De Santiago De Compostela	Santiago De Compostela	Spain
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hospital Universitario 12 De Octubre	Madrid	Spain
Area De Salud De Burgos Y Soria	Burgos	Spain
Institut de Cancérologie de l’Ouest	Saint-Herblain	France
Hkilbatw Uzjcqxgrfbjch Mrnidpk Df Vnkubppkxk	Santander	Spain
Fgwlmahzj Pweo Ll Ibqnnbsaabbxn Btxguzhps Doe Hpsuhfrp Usqssyywruune Lc Pdg	Madrid	Spain
Hxjvxwbr Uoacqhguxelri Hkywxqkt Trekx y Pwpuvr Ibfmhlmz Cphnmf dfxxqmswnwjacxehd (galo	Badalona	Spain
Hkighpfp Vwzl dnrlrrnd	Barcelona	Spain
Cfzarx Oitxg Liyfahq	Lille	France

Trial status

Country	Status	Recruitment Start
France	Not recruiting	15.10.2025
Spain	Not recruiting	15.10.2025

Trial locations

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.

Investigated diseases:

Neuroendocrine carcinoma

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 ID:

2024-514327-42-00

Trial Phase:

Therapeutic exploratory (Phase II)

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

What is this study about?

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