Study Comparing Tarlatamab, Durvalumab, Carboplatin, and Etoposide versus Durvalumab, Carboplatin, and Etoposide in First-Line ES-SCLC (DeLLphi-312)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Sep 2025 → ongoing

Decision date (initial)

2025-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520050-38-00

WHO UTN

U1111-1320-9851

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy

Primary: Compare the efficacy of tarlatamab in combination with durvalumab, carboplatin and etoposide to the combination of durvalumab, carboplatin and etoposide on
prolonging overall survival (OS).

Secondary objectives 6

1. Secondary: Compare the efficacy of tarlatamab in combination with durvalumab, carboplatin and etoposide to the combination of durvalumab, carboplatin and etoposide as assessed by progression free survival (PFS) based on investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
2. Secondary: Compare the efficacy of tarlatamab in combination with durvalumab, carboplatin and etoposide to the combination of durvalumab, carboplatin and etoposide as assessed by objective response (OR), disease control (DC) and duration of response (DOR) based on BICR and investigator assessment per RECIST 1.1
3. Secondary: Compare the efficacy of tarlatamab in combination with durvalumab, carboplatin and etoposide to the combination of durvalumab, carboplatin and etoposide asassessed by: o PFS at 6 months, 1 year, and 2 years from randomization based on BICR and investigator assessment per RECIST 1.1 o OS at 6 months, 1 year, 2 years, and 3 years from randomization o Time to progression (TTP) based on BICR and investigator assessment per RECIST 1.1
4. Secondary: Compare the safety and tolerability of tarlatamab in combination with durvalumab, carboplatin, and etoposide to the combination of durvalumab, carboplatin and etoposide.
5. Secondary: Characterize the pharmacokinetics (PK) of tarlatamab when administered in combination with durvalumab, carboplatin and etoposide.
6. Secondary: Evaluate the immunogenicity of tarlatamab.

Conditions and MedDRA coding

Extensive stage small cell lung cancer (ES-SCLC). Small-cell lung cancer, accounting for 10% to 15% of lung cancer (Rudin et al, 2015), is an aggressive lung cancer subtype with neuroendocrine differentiation and strongly associated with smoking (Koinis et al, 2016). It displays a distinct natural history characterized by a high growth fraction, rapid doubling time and early establishment of widespread metastatic lesions (Gustafsson et al, 2008). Around 70% of patients are diagnosed with ES-SCLC, presenting with distant metastasis or tumor or nodal volume that is too large to be encompassed in a tolerable radiation plan.

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant has provided informed consent before initiation of any study-specific activities/procedures.
2. Age ≥ 18 years or ≥ legal age within the country if it is older than 18 years.
3. Histologically or cytologically documented extensive-stage small-cell lung cancer (American Joint Committee on Cancer, 2017, Stage IV SCLC [T any, N any, M1 a/b/c]), or T3 to T4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.
4. Measurable disease as defined per RECIST 1.1
5. No prior treatment for SCLC. NOTE: (see section 5.1 of the Protocol for additional details)
6. Suitable to receive carboplatin, etoposide and durvalumab regimen as first-line treatment per investigator clinical assessment.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
8. Minimum life expectancy ≥ 12 weeks.
9. Adequate organ function, defined as follows:  Hematological function: o Absolute neutrophil count ≥ 1.5 x 10^9/L o Platelet count ≥ 100 x 10^9/L o Hemoglobin ≥ 9 g/dL (90 g/L)  Coagulation function: o Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) ≤ 1.5 x institutional upper limit of normal (ULN) except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 2 weeks prior to randomization  Renal function: o Estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 60 mL/min/1.73 m2  Hepatic function: o aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (or ≤ 5 x ULN for participants with liver involvement) o Total bilirubin (TBL) ≤ 1.5 x ULN (or ≤ 2 x ULN for participants with liver involvement), with the exception of participants with Gilbert's disease  Pulmonary function: o No oxygen supplementation  Cardiac function: o Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) [or multigated acquisition (MUGA) scan if ECHO is not available], and no electrocardiogram (ECG) finding related to acute/subacute myocardial ischemia and/or clinically significant arrythmia.

Exclusion criteria 28

1. Symptomatic central nervous system (CNS) metastases, or leptomeningeal disease.
2. History of allergic reactions or acute hypersensitivity reactions to antibody therapies, carboplatin, etoposide or pegfilgrastim.
3. Participant with symptoms and/or signs of systemic infection requiring parental oral antibiotics within 7 days prior to the first dose of study treatment.
4. Prior history of severe or life-threatening events from any immune-mediated therapy.
5. Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment (see Protocol section 5.2 for additional details).
6. Treatment with live virus, including live-attenuated vaccination, within 4 weeks prior to the first dose of study treatment. Inactive vaccines (eg, non-live or nonreplicating agent) and live viral non-replicating vaccines (eg,Jynneos for mpox infection) within 3 days prior to first dose of study treatment.
7. Receiving another anticancer therapy for a malignancy other than SCLC. Adjuvant hormonal therapy for resected breast cancer is permitted.
8. History of other malignancy within the past 2 years, with the following exceptions (see Protocol 5.2 for exceptions)
9. Active or prior documented autoimmune or inflammatory disorders
10. Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months prior to first dose of study treatment.
11. History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months prior to first dose of study treatment.
12. Evidence of interstitial lung disease (ILD) or active, non-infectious pneumonitis.
13. History of solid organ transplant.
14. Major surgical procedures within XX days prior to first dose of study treatment.
15. Presence of active HIV or active hepatitis infection.
16. Has received or is planning to receive consolidative chest radiation, for extensive-stage disease.
17. Participation in a tarlatamab clinical trial or prior therapy with any selective inhibitor of the DLL3 pathway.
18. Treatment in an alternative investigational trial within XX days prior to enrollment.
19. Participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional (see Protocol section 5.2 for details).
20. Participants who are breastfeeding or who plan to breastfeed while on study through (see Protocol section 5.2 for details).
21. Participants planning to become pregnant while on study through (see Protocol section 5.2 for details).
22. Participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive urine or serum pregnancy test.
23. Participants with a partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional (see Protocol section 5.2 for details).
24. Participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional (see Protocol section 5.2 for details).
25. Participants unwilling to abstain from donating sperm during treatment and for an additional (see Protocol section 5.2 for details).
26. Participant has known sensitivity to any of the products or components to be administered during dosing.
27. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the Participant and investigator’s knowledge. Participants who are unable to complete clinical outcome assessments questionnaires are eligible.
28. History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety, or interfere with the study evaluation, procedures or completion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. OS
2. Progression free survival (BICR assessed)

Secondary endpoints 6

1. PFS
2. OR, DC, DOR
3. PFS rate at 6 months, 1 year, and 2 years from randomization OS rate at 6 months, 1 year, 2 years, and 3 years from randomization TTP
4. Incidence of treatment-emergent adverse events
5. Serum concentrations of tarlatamab.
6. Incidence of anti-tarlatamab antibody formation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1730

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 8

Locations

13 EU/EEA countries · 59 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 106 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications