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

NCT07203053 | Recruiting Phase 2 DMC

• 1 other identifier: ETOP 29-25
• Study Type: interventional
• Target: 48
• Locations: 5 countries
• Sites: 19

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

Keywords

ES-SCLC; Tarlatamab

Outcome Measures

Primary Outcomes (1)

• Overall survival rate at 12 months (12-month OS)

  The OS rate at 12 months is the primary endpoint of the trial. It is defined as the proportion of patients who are alive at 12 months from enrolment. The rate will be calculated as the number of patients alive at 12 months divided by the number of patients on follow-up at 12 months or with an earlier observed death event.

  OS is defined as the time from the date of enrolment until death from any cause. Assessed for approximately up to 41 months.

Secondary Outcomes (5)

• Objective response rate (ORR)

  Assessed for approximately up to 41 months.

• Duration of response (DoR)

  Assessed for approximately up to 41 months.

• Disease control rate (DCR)

  Assessed for approximately up to 41 months.

• Progression-free survival (PFS)

  Assessed for approximately up to 41 months.

• Incidence, nature, and severity of adverse events

  Assessed for approximately up to 41 months.

Study Arms (1)

Tarlatamab

EXPERIMENTAL

Drug: Tarlatamab

Interventions

Tarlatamab 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.

Tarlatamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Amgen: collaborator

Study Sites (19)

CHU Angers

Angers, France

NOT YET RECRUITING

Institut Bergonie

Bordeaux, France

NOT YET RECRUITING

Lyon - Centre Léon Bérard

Lyon, France

NOT YET RECRUITING

Hôpital Nord de Marseille

Marseille, France

NOT YET RECRUITING

Henry Dunant Hospital Center

Athens, Greece

NOT YET RECRUITING

Irccs Irst

Meldola, Italy

NOT YET RECRUITING

Instituto Europeo di Oncologia (IEO)

Milan, Italy

NOT YET RECRUITING

Santa Maria della Misericordia Hospital

Perugia, Italy

NOT YET RECRUITING

AO San Giovanni Addolorata

Roma, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori "Regina Elena"

Roma, Italy

NOT YET RECRUITING

Hospital General Universitario Alicante

Alicante, Spain

NOT YET RECRUITING

Hospital de la Santa Creu I Sant Pau

Barcelona, Spain

NOT YET RECRUITING

Hospital Universitatrio Vall d'Hebron

Barcelona, Spain

NOT YET RECRUITING

ICO Hospitalet H. Duran I Reynals / H. Bellvitge

Barcelona, Spain

NOT YET RECRUITING

Hospital Universitatrio Puerta del Hierro

Madrid, Spain

NOT YET RECRUITING

Kantonsspital Baden

Baden, Switzerland

RECRUITING

HFR - Hôpital cantonal

Fribourg, Switzerland

NOT YET RECRUITING

Geneva University Hospitals

Geneva, Switzerland

RECRUITING

Kantonsspital St.Gallen

Sankt Gallen, Switzerland

NOT YET RECRUITING

Study Officials

• Maurice Pérol, MD

  Centre Léon Bérard, Lyon, France

  STUDY CHAIR

• Federico Capuzzo, MD

  IRCCS Regina Elena, Rome, Italy

  STUDY CHAIR

Central Study Contacts

Heidi Roschitzki, PhD

CONTACT

+41 31 511 94 00; heidi.roschitzki@etop.ibcsg.org

Susanne Roux

CONTACT

+41 31 511 94 00; START-lung@etop.ibcsg.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: October 2, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

IT (5); FR (4); GR (1); CH (4); ES (5)