Phase 3 Study of Subcutaneous vs Intravenous Tarlatamab with Siltuximab in Relapsed Extensive-Stage Small Cell Lung Cancer after Platinum Chemotherapy

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What is this study about?

The study focuses on people whose cancer has returned after initial treatment and who have Extensive-Stage Small Cell Lung Cancer, a lung cancer that has spread widely. The medicine being tested is called Tarlatamab, which is given either as an under‑skin injection (subcutaneous) or as a drip into a vein (intravenous). The drug works by helping the body’s immune system find and attack the cancer cells.

The purpose of the study is to find out if the under‑skin injection works at least as well as the vein infusion in terms of how the drug moves through the body (pharmacokinetic). Participants are randomly assigned to one of the two ways of receiving the medicine and will visit the clinic regularly for blood tests, imaging scans to see the tumor, and safety checks. The trial lasts for several months, during which any side effects are recorded and managed.

1 enrollment and randomization

after joining the study you will be assigned randomly to receive tarlatamab by either the subcutaneous (under the skin) route or the intravenous (through a vein) route.

the assignment is made by the study team and you will be informed which method you will receive.

2 baseline assessments

initial medical examinations, imaging scans of the tumor, and blood tests are performed to record your condition before treatment starts.

these results are used as reference points for later comparisons.

3 first dose of tarlatamab

if you are assigned to the subcutaneous group you will receive a single injection of tarlatamab at a dose of 9999 mg.

if you are assigned to the intravenous group you will receive a single infusion of tarlatamab at a dose of 10 mg.

4 background medication

you will also receive siltuximab by the intravenous route at a dose of 2500 mg.

this medication is given in addition to the study drug as part of the trial protocol.

5 subsequent treatment cycles

tarlatamab is administered at the start of each treatment cycle for the duration of the study.

the same dose and route that you received at the first administration (9999 mg subcutaneous or 10 mg intravenous) are used for each cycle.

the exact length of each cycle is defined by the study schedule.

6 pharmacokinetic blood sampling

blood samples are taken to measure how the drug behaves in your body.

samples are collected from day 1 to day 15 of the second cycle and a predose sample is taken on day 15 of the second cycle.

7 tumor response assessments

imaging scans are repeated at scheduled intervals to evaluate changes in tumor size.

the assessments follow the response evaluation criteria in solid tumors version 1.1 (recist v1.1) guidelines.

8 safety monitoring

throughout the trial you are monitored for any adverse events, including side effects that may be serious or require medical attention.

all events are recorded and evaluated by the study team.

9 final visit and study completion

at the end of the trial period a final assessment is performed, including the last set of blood tests, imaging, and safety evaluations.

after this visit the study participation is concluded.

Who Can Join the Study?

You must sign an informed consent form before any study procedures begin, which means you agree to take part after understanding what will happen.
Any side effects from previous cancer treatment must have improved to mild (grade 1) or lower, except for hair loss (any level), fatigue up to moderate (grade 2), anemia up to moderate (grade 2) with a hemoglobin level of at least 9 g/dL, and hypothyroidism up to moderate (grade 2) that is being treated with hormone replacement.
You must be at least 18 years old (or the legal adult age in your country if it is higher).
You need a confirmed diagnosis of small‑cell lung cancer by tissue testing, and the cancer must have gotten worse or come back after one course of platinum‑based chemotherapy (with or without a PD‑(L)1 immunotherapy drug). If your first treatment included a PD‑(L)1 drug, you must have stopped responding to it or be unable to receive it. Patients whose earlier cancer was limited‑stage but relapsed within 6 months after the last platinum dose may also qualify.
Your disease must be measurable on scans according to the RECIST 1.1 guidelines during the 21‑day screening period.
If you have a history of cancer spread to the brain or spinal fluid (CNS metastases), you may still be eligible if:
- Untreated brain spots are not causing symptoms, do not need corticosteroids (steroid medicines) or anticonvulsants (seizure medicines), and the doctor believes they do not need immediate local treatment.
- Treated brain spots are allowed if radiation was finished at least 14 days ago (or at least 7 days after stereotactic radiosurgery), you have only mild (grade 1) side effects from radiation, and you are on a low dose of steroids (no more than 10 mg prednisone or equivalent per day) or seizure medicine.
- You must not have cancer spreading to the lining of the brain and spinal cord (leptomeningeal carcinomatosis).
You must have an available sample of tumor tissue from the time of diagnosis (archival tumor tissue). If none is available, a new biopsy must be taken during screening unless it is unsafe, in which case the doctor can explain why.
Your overall health level must be an ECOG performance status of 0 or 1, meaning you are fully active or have only mild symptoms.
The doctor must judge that you have a minimum life expectancy of at least 12 weeks.
You must have adequate function of your blood, clotting, kidneys, liver, lungs, and heart (organ function) as shown by the study’s lab tests.

Who Cannot Join the Study?

Having previously been diagnosed with non‑small cell lung cancer (NSCLC) that had an epidermal growth factor receptor (EGFR) activating mutation and later changed to small cell lung cancer, or having a tumor that contains both NSCLC and small cell types where the NSCLC part carries an EGFR‑activating mutation.
Having received more than one previous line of chemotherapy or other anticancer treatment for small cell lung cancer.
Having taken part in any earlier tarlatamab study or having received any drug that blocks the DLL3 pathway.
Being known to be allergic or having a medical reason not to receive any of the medicines or ingredients used in the study.
Being enrolled in a different experimental trial within the 28 days before starting this study.
Having had another type of cancer (not small cell lung cancer) within the past two years, except for certain skin cancers, cervical carcinoma in situ, breast ductal carcinoma in situ, non‑cancerous prostate changes, or non‑invasive bladder cancers that have been fully treated.
Having uncontrolled fluid buildup around the lungs (pleural effusion), heart (pericardial effusion), or abdomen (ascites) that needs to be drained more than once a month.
Having had a major surgical operation within 28 days before the first dose of the study drug.
Having experienced a severe or life‑threatening reaction to any therapy that works by affecting the immune system.
Taking systemic corticosteroids (steroid medicines that affect the whole body) or any other immune‑suppressing drugs within 14 days before the first dose.
Receiving any live‑virus vaccine, live‑attenuated vaccine, or certain non‑live viral vaccines (such as JYNNEOS®) within 28 days before the first dose.
Having a current or past infection with viral hepatitis (liver inflammation caused by hepatitis viruses).
Having previously received a solid organ transplant (such as a kidney, liver, or heart transplant).
Having an allergy or hypersensitivity to drugs that are similar in structure, other monoclonal antibodies, or any of the inactive ingredients (excipients) in the study medication.
Being unable to receive a subcutaneous (under‑the‑skin) injection in the abdomen or thigh.
Being judged by the doctor as unlikely to complete all required study visits, tests, and procedures.
Having any other serious medical condition that the investigator believes could put your safety at risk during the study.
Showing signs of an active, uncontrolled infection in the body (such as fever, cough, or positive test) within 7 days before the first dose.
Having taken any systemic anticancer therapy within 30 days before enrolling in the study.
Having had a heart attack (myocardial infarction) or symptomatic congestive heart failure that is more severe than NYHA class II (moderate to severe limitation of activity) within the past 6 months. (A stable, treated atrial fibrillation is allowed.)
Having experienced an arterial blood clot event such as a stroke, loss of blood flow to a limb, kidney, or intestine within the past 6 months. (A single, fully resolved transient ischemic attack (TIA) may be allowed.)
Having current or past non‑infectious lung inflammation (pneumonitis or interstitial lung disease) that required steroids or other immune‑suppressing treatment.
Receiving another anticancer therapy for a cancer other than small cell lung cancer (except for hormone therapy after breast cancer surgery).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Koranyi National Institute For Pulmonology	Budapest	Hungary
Oncopole Claudius Regaud	Toulouse	France
Katholieke Universiteit te Leuven	Leuven	Belgium
Hospital Universitario Y Politecnico La Fe	Valencia	Spain

Other Sites

Site Name	City	Country
Az St-Jan Brugge-Oostende A.V.	Brugge	Belgium
Centre Hospitalier Universitaire De Nantes	Nantes	France
Complejo Hospitalario Universitario Insular Materno Infantil	Las Palmas De Gran Canaria	Spain
Cxulnqhbz Urzlpijduwnult Slynksfqe	Woluwe-Saint-Lambert	Belgium
Maujnl Ggiquedztgiq	Gyongyos	Hungary
Anzowwinx Uaz	Amsterdam	The Netherlands
Atliactefq Peuzuczd Hrduiova Dp Mjvpkslhx	Marseille	France
Uuqlhgsbatry Mthiwcy Cboypsv Ueihehv	Utrecht	The Netherlands
Bmfytcdk Ubtpipvqdh Hbtdibni Cvrhhn	Besançon	France
Eqchlfp Uvszetzipenh Mflppsh Cqngski Rcohwknjv (xgdcdyv Mcf	Rotterdam	The Netherlands
Sfcwjtkol Rnmgayf Ufqhewcfyd Mrqyfmg Ciapel	Nijmegen	The Netherlands
Joxbq Zchdinadci	Hasselt	Belgium
Hfvgdhho Cjw Tksu Shdk	Lisbon	Portugal
Twvnbzdvelplpqwao Twznzfaaqzfvq	Torokbalint	Hungary
Ciqihw Hnolvbavjgl Ugymlhonoewea Dv Rxgzqk	Rennes	France
Cnvjfl Hocemjubne Uxvyhfgohujdp Dr Secrt Agykjby Exbasr	Porto	Portugal
Ibysk Kpldkjlsy Sgczmtxrb	Zwolle	The Netherlands
Cweuos Hsvebueblpi Lvfj Sih	Pierre Benite	France
Amjpccbz Zcvfjombmf Dnhgq	Roeselare	Belgium
Croluc Hdkibyhyken Uyrdeaiqhvpfz Dcpbgu Gtgnjqz Ssbtxjkffvjqpadwysysgbdbmj	Namur	Belgium
Aqpqezzj Zrpnltnhvi Gimuxrjqj	Kortrijk	Belgium
Ejlrvoa	Mechelen	Belgium
Czjg Ccpkwf Cpkjtdr Agrfmhyxp Baaxe Aqxslsbmes	Braga	Portugal
Ukgwvfm Lmthw Dk Srdtr Dv Mpscinogbx Edzzxk	Senhora Da Hora	Portugal
Huqtnblg Vwgi dbsjmlva	Barcelona	Spain
Hbohakdi Ualfxqiitugnn dc A Cpcchy	A Coruna Galicia	Spain
Iivafrqf Dk Cepszfjt Fysolcpjic Dmh Psasdmcj Pvk Lihxrwdycl Ixerr	Candiolo	Italy
Heqdmlvh Df Lb Sxawh Cxdl I Sdtr Piq	Barcelona	Spain
Criltp Rmugiwpd Cpzdrcll Df Vjrmlj Sgnxej	Verona	Italy
Hgmxyoia Uycirtvqdphrv Ptcpxp Do Hohdhc Dt Mrmjzvprrpa	Majadahonda	Spain
Hyxquwam Uxylxdefxgrxb 1t Dc Oimwhyr	Madrid	Spain
Acervha Otttsqrjtrb S Gnuxxnav Arrocamexp	Rome	Italy
Iatxnnam Twoxzh Bttq Ggouxaco Pmuvz Ig	Bari	Italy
Fohshnvnot Icppjqzfxi Irhhtnmu Neiitqqwqob Btrgc	Milan	Italy

Trial status

Country	Status	Recruitment Start
Belgium	Not yet recruiting	31.08.2026
France	Not yet recruiting	31.08.2026
Hungary	Not yet recruiting	31.08.2026
Italy	Not yet recruiting	31.08.2026
Portugal	Not yet recruiting	31.08.2026
Spain	Not yet recruiting	31.08.2026
The Netherlands	Not yet recruiting	31.08.2026

Trial locations

Investigated Drugs:

Tarlatamab is a medication being studied as a treatment for relapsed extensive‑stage small cell lung cancer. In this trial participants receive it either as an injection under the skin (subcutaneous) or as an infusion into a vein (intravenous). The study’s main goal is to see whether the under‑skin injection gives similar drug levels in the body compared with the IV infusion, which could make treatment easier for patients. Tarlatamab is an orphan‑drug, meaning it is intended for a rare condition.

Siltuximab is an antibody that blocks a protein that can help cancer cells grow and cause inflammation. In this study it is given to all participants as background therapy, so it is part of the standard treatment that patients receive while the main focus is on testing Tarlatamab. Its role is to support the overall treatment plan without being the primary drug being evaluated.

Investigated Diseases:

Small cell lung cancer extensive stage

Relapsed extensive-stage small cell lung cancer – It is a type of lung cancer that originates from neuroendocrine cells and spreads quickly throughout the lungs and other organs. Extensive-stage means the disease has already spread beyond the lung at initial diagnosis. After initial platinum‑based chemotherapy, the cancer can return, which is described as relapsed. When it returns, the tumor often grows again in the lungs and may appear in the liver, brain, or bones. The disease continues to progress as cancer cells multiply and invade new sites.

Trial ID:

2026-525489-23-00

Protocol code:

20250046

Trial Phase:

Therapeutic confirmatory (Phase III)

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Phase 3 Study of Subcutaneous vs Intravenous Tarlatamab with Siltuximab in Relapsed Extensive-Stage Small Cell Lung Cancer after Platinum Chemotherapy

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?