A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects with SCLC

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

10 Jun 2025 → ongoing

Decision date (initial)

2025-05-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-516051-40-00

WHO UTN

U1111-1313-6161

ClinicalTrials.gov

NCT06745323

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacokinetic, Efficacy, Safety

Evaluate the efficacy of tarlatamab on ORR based on blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary objectives 6

1. Characterize the pharmacokinetics (PK) of tarlatamab
2. Evaluate efficacy of tarlatamab as assessed by additional measures per RECIST 1.1 by BICR
3. Evaluate anti-tumor activity of tarlatamab as determined by other measures per RECIST 1.1 by investigator
4. Evaluate efficacy of tarlatamab by OS
5. Evaluate the safety and tolerability of tarlatamab
6. Evaluate the immunogenicity of tarlatamab

Conditions and MedDRA coding

Small Cell Lung Cancer (SCLC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

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 8

1. Subject has provided informed consent before initiation of any study-specific activities/procedures. Exception: Standard of care imaging and laboratory assessments performed prior to informed consent.
2. Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent.
3. Histologically or cytologically confirmed SCLC with demonstrated progression or relapse.
4. Subject has progressed or recurred following 1 platinum-based regimen. In countries where standard of care first-line systemic treatment for ES disease includes platinum-containing chemotherapy in combination with PD-(L)1 inhibitor, it is required that subjects have failed PD-(L)-1 inhibitor as part of their first-line systemic treatment or are ineligible to receive PD-(L)1 inhibitor therapy.
5. Measurable disease at baseline per RECIST 1.1 within the 21-day screening period. - Screening scans performed as standard of care and prior to informed consent, may be used to confirm subject eligibility if completed within the 21-day screening period, provided that informed consent for the use of these scans is obtained prior to any transfer of data.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Minimum life expectancy of 12 weeks.
8. Adequate organ function, defined as follows: Refer to protocol section 5.1 for more details. - Hematological function: - Coagulation function: - Renal function: - Hepatic function: - Pulmonary function: -Cardiac function:

Exclusion criteria 27

1. Any previous diagnosis of transformed non-small cell lung cancer (NSCLC) including epidermal growth factor receptor activating mutation positive NSCLC that has transformed to SCLC
2. History of other malignancy within the past 2 years (see protocol section 5.2 for exceptions)
3. Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study(ies). Other investigational procedures and participation in observational research studies while participating in this study are excluded
4. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
5. Female subjects of childbearing potential unwilling to use protocol-specified method of contraception during treatment & for an additional XX days after the last dose of tarlatamab
6. Female subjects who are breastfeeding or who plan to breastfeed while on study through XX days after the last dose of tarlatamab.
7. Female subjects planning to become pregnant or donate eggs while on study through XX days after the last dose of tarlatamab.
8. Diagnosis or evidence of leptomeningeal disease
9. 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
10. History of solid organ transplantation.
11. Prior anticancer therapy within 30 days of enrollment (14 days for conventional chemotherapy
12. Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study treatment. Inactive vaccines (eg, non-live or non-replicating agent) and live viral non-replicating vaccines (eg, Jynneos for Monkeypox infection) within 3 days prior to first dose of study treatment
13. Prior enrollment on a tarlatamab clinical trial OR prior therapy with any selective inhibitor of the DLL3 pathway.
14. Receiving other anti-cancer therapy such as chemotherapy, immunotherapy, or targeted therapy. Subjects who are receiving adjuvant hormonal therapy for resected breast cancer may be eligible (refer also to exclusion related to history of other malignancies).
15. Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to first dose of study treatment (see protocol section 5.2 for exceptions)
16. Female subjects of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 by a highly sensitive urine or serum pregnancy test
17. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment & for an additional XX days after the last dose of tarlatamab
18. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional XX days after the last dose of tarlatamab
19. Male subjects unwilling to abstain from donating sperm during treatment & for an additional XX days after the last dose of tarlatamab
20. Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months prior to first dose of study treatment
21. History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months prior to first dose of study treatment
22. Prior history of severe or life-threatening events from any immune-mediated therapy
23. Major surgical procedures within 21 days prior to first dose of study treatment
24. Presence or history of viral infection: Human immunodeficiency virus (HIV) infection, Active hepatitis B or C infection
25. Subject 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
26. Symptomatic central nervous system (CNS) metastases (see protocol section 5.2 for exceptions)
27. Subject has known sensitivity to any of the products or components to be administered during dosing

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Confirmed OR (CR + PR)
2. CR (Complete Response)
3. PR (Partial Response)

Secondary endpoints 10

1. serum concentrations of tarlatamab
2. DOR - Duration of confirmed response
3. DC -Disease control is defined as objective response or stable disease.
4. Duration of DC
5. PFS-Progression-free survival
6. OR - Objective response is defined as best overall response of CR or PR.
7. Overall survival (OS) -Overall survival is defined as the time from randomization to death due to any cause.
8. OS rate at 6 months and 1 year from randomization
9. Incidence of treatment-emergent adverse events
10. Incidence of anti-tarlatamab antibody formation

Investigational products

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

Test 2

Auxiliary 1

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 17

Locations

6 EU/EEA countries · 23 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 57 files

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

Application history

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