A Trial of Tarlatamab in Patients With Pretreated Extensive-stage Small Cell Lung Cancer (ES-SCLC) and ECOG PS 2

NCT ID: NCT07203053

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-31
• Study Completion Date: 2029-10-31

Brief Summary

START-lung is an international, multicentre, single-arm phase II trial. Protocol treatment consists of tarlatamab administered as an intravenous infusion until disease progression according to RECIST v1.1 criteria, unacceptable toxicity, or patient decision, whichever comes first. The primary objective of the trial is to assess the clinical efficacy of tarlatamab, in terms of 12-month OS rate, in patients with ES-SCLC and ECOG PS 2 who have previously received only one line of platinum-etoposide doublet chemotherapy with immune-checkpoint inhibition and whose disease has progressed.

Conditions

Extensive Stage Lung Small Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tarlatamab

Group Type: EXPERIMENTAL

Tarlatamab

Intervention Type: DRUG

Protocol treatment consists of tarlatamab, administered as an intravenous (i.v.) infusion:

• 1 mg on day 1 (C1D1),
• 10 mg on day 8 (C1D8) and
• 10 mg on day 15 (C1D15),
• then 10 mg every two weeks (Q2W) until disease progression according to RECIST v1.1 criteria, unacceptable toxicity, or patient decision, whichever comes first.

Interventions

Tarlatamab

Protocol treatment consists of tarlatamab, administered as an intravenous (i.v.) infusion:

• 1 mg on day 1 (C1D1),
• 10 mg on day 8 (C1D8) and
• 10 mg on day 15 (C1D15),
• then 10 mg every two weeks (Q2W) until disease progression according to RECIST v1.1 criteria, unacceptable toxicity, or patient decision, whichever comes first.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed ES-SCLC.
• Previous treatment with only one line of platinum-etoposide doublet chemotherapy with immune-checkpoint inhibition for SCLC.

Patients treated with a platinum-etoposide doublet chemotherapy for prior limited stage (LS)-SCLC may be eligible for the study if the disease has progressed on treatment or within 6 months from chemotherapy completion (i.e. during durvalumab consolidation): the platinum-etoposide line of therapy will count as one prior line of therapy.

• Progressive disease on or after the first-line treatment for SCLC.
• ECOG Performance Status 2.
• Age ≥18 years.
• Adequate haematological, renal and liver function.
• Coagulation function: Prothrombin time (PT)/international normalised ratio (INR) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5x ULN, except for patients receiving anticoagulation, who must be on a stable dose of anticoagulation therapy for 6 weeks prior to enrolment.
• Pulmonary function:

• No clinically significant pleural effusion. Pleural effusion managed with indwelling pleural catheter (e.g., PleurX) are allowed.
• Baseline oxygen saturation >90% on room air.
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan (preferred), and no clinically significant electrocardiogram (ECG) findings.
• Women of childbearing potential, must have a negative urinary or serum pregnancy test within 5 weeks before enrolment. Pregnancy test must be repeated within 3 days before the first dose of tarlatamab treatment.
• Written Informed Consent must be signed and dated by the patient and the investigator prior to any trial-related intervention.

Exclusion Criteria

• Symptomatic CNS metastases Patients with untreated asymptomatic brain metastases and patients with treated and stable brain metastases are eligible.
• Diagnosis or evidence of leptomeningeal disease or spinal cord compression
• Prior history of immune-checkpoint inhibitor treatment resulting in:

• any severe or life-threatening immune-mediated adverse event,
• history of immune-mediated encephalitis or another immune-mediated CNS event (any grade),
• grade ≥2 immune-mediated recurrent pneumonitis,
• infusion-related reactions leading to permanent discontinuation of the immunotherapy agent.

Exception: patients with a history of immune-checkpoint inhibitor-induced endocrinopathy which is clinically stable on replacement therapy.

• Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.
• History of solid organ transplantation.
• Treatment with live virus, including live-attenuated vaccination within 14 days prior to enrolment and inactive vaccines (e.g., non-live or non-replicating agent) and live viral non-replicating vaccines (e.g., Jynneos for Monkeypox infection) within 3 days prior to enrolment.
• History of other malignancy within the past 2 years, with the following exceptions:

• Low-risk malignancy treated with curative intent and with no known active disease present for ≥1 year before enrolment and believed to be at low risk for recurrence per investigator discretion.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ.
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association >class II) within 12 months prior to enrolment.
• History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 12 months prior to enrolment.
• Presence/history of an uncontrolled viral infection:

• Known uncontrolled human immunodeficiency virus (HIV) infection.
• Active hepatitis C infection (patients with detectable hepatitis C antibody [HCV Ab] and HCV RNA viral load above the limit of quantification).
• Patients with presence of HCV Antibodies and HCV RNA viral load below the limit of quantification (HCV RNA negative) with or without prior treatment are allowed.
• Active hepatitis B infection (presence of hepatitis B surface antigen [HBsAg] and hepatitis B virus [HBV] DNA viral load above the limit of quantification [HBV DNA positive]).
• Patients with resolved HBV infection defined as absence of HBsAg and presence of HBV core antibody (anti-HBc) followed by an HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
• Patients with chronic HBV infection inactive carrier state defined as presence of HBsAg and HBV DNA viral load below the limit of quantification [HBV DNA negative] are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
• Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to first dose of study treatment.

• Prophylactic dexamethasone for the management of tarlatamab-related adverse events and any anti-emetic therapies are allowed.
• Low-dose corticosteroids (prednisone ≤10 mg per day or equivalent) is permitted during the trial.
• Patients with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of study treatment.

• Patient has known active infection requiring parenteral antibiotic treatment. Upon completion of parenteral antibiotics and resolution of symptoms, the patient may be considered eligible for the study from an infection standpoint.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Major surgical procedures within 5 weeks prior to enrolment.
• Any concurrent medical condition which, in the opinion of the investigator, would compromise patient safety or interfere with the evaluations for tarlatamab.
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• Women who are pregnant or in the period of lactation.
• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial until at least 60 days after the last dose of tarlatamab treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maurice Pérol, MD

Role: STUDY_CHAIR

Centre Léon Bérard, Lyon, France

Federico Capuzzo, MD

Role: STUDY_CHAIR

IRCCS Regina Elena, Rome, Italy

Locations

CHU Angers

Angers, , France

Institut Bergonie

Bordeaux, , France

Lyon - Centre Léon Bérard

Lyon, , France

Hôpital Nord de Marseille

Marseille, , France

Henry Dunant Hospital Center

Athens, , Greece

Irccs Irst

Meldola, , Italy

Instituto Europeo di Oncologia (IEO)

Milan, , Italy

Santa Maria della Misericordia Hospital

Perugia, , Italy

AO San Giovanni Addolorata

Roma, , Italy

Istituto Nazionale Tumori "Regina Elena"

Roma, , Italy

Hospital General Universitario Alicante

Alicante, , Spain

Hospital de la Santa Creu I Sant Pau

Barcelona, , Spain

Hospital Universitatrio Vall d'Hebron

Barcelona, , Spain

ICO Hospitalet H. Duran I Reynals / H. Bellvitge

Barcelona, , Spain

Hospital Universitatrio Puerta del Hierro

Madrid, , Spain

Kantonsspital Baden

Baden, , Switzerland

HFR - Hôpital cantonal

Fribourg, , Switzerland

Geneva University Hospitals

Geneva, , Switzerland

Kantonsspital St.Gallen

Sankt Gallen, , Switzerland

Countries

France; Greece; Italy; Spain; Switzerland

Central Contacts

Heidi Roschitzki, PhD

Role: CONTACT

heidi.roschitzki@etop.ibcsg.org

+41 31 511 94 00

Susanne Roux

Role: CONTACT

START-lung@etop.ibcsg.org

+41 31 511 94 00

Facility Contacts

Youssef Oulkhouir

Role: primary

Sophie Cousin

Role: primary

Maurice Perol

Role: primary

Laurent Greillier

Role: primary

Giannis Mountzios

Role: primary

Angelo Delmonte

Role: primary

Filippo de Marinis

Role: primary

Giulio Metro

Role: primary

Antonio Lugini

Role: primary

Federico Capuzzo

Role: primary

Juan Luis Martí

Role: primary

Andrés Barba Joaquin

Role: primary

Pedro Rocha

Role: primary

Miguel Ángel Mosteiro Lamas

Role: primary

Mariano Provencio

Role: primary

Sacha Rothschild

Role: primary

Adrienne Bettini

Role: primary

Alfredo Addeo

Role: primary

Kira-Lee Koster

Role: primary

Other Identifiers

ETOP 29-25

Identifier Type: -

Identifier Source: org_study_id