Study Evaluating Tarlatamab After Chemoradiotherapy in Limited‑Stage Small‑Cell Lung Cancer (DeLLphi-306)

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

7 Nov 2024 → ongoing

Decision date (initial)

2024-06-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-506235-15-00

WHO UTN

U1111-1296-8969

ClinicalTrials.gov

NCT06117774

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Therapy

Compare the efficacy of tarlatamab with placebo as assessed by progression free survival (PFS) based on blinded independent central review (BICR) per RECIST 1.1

Compare the efficacy of tarlatamab with placebo on prolonging overall survival (OS)

Secondary objectives 6

1. Describe the efficacy of tarlatamab and placebo as assessed by PFS based on investigator assessment per RECIST 1.1
2. Describe the efficacy of tarlatamab and placebo as assessed by - PFS at 6 months, 1 year and 2 years from randomization based on BICR and investigator assessment per RECIST 1.1 - OS at 6 months, 1 year, 2 years and 3 years from randomization - Time to progression (TTP) based on BICR and investigator assessment per RECIST 1.1
3. Examine the safety and tolerability of tarlatamab and placebo
4. Characterize the pharmacokinetics (PK) of tarlatamab
5. Evaluate the immunogenicity of tarlatamab
6. Describe the efficacy of tarlatamab and placebo as assessed by complete response (CR), and duration of complete response based on BICR and investigator assessment per RECIST 1.1

Conditions and MedDRA coding

Limited-Stage Small-Cell Lung Cancer (LS SCLC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

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. Subject has provided informed consent prior to 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 confirmed SCLC.
4. Diagnosed and treated for LS-SCLC with concurrent chemotherapy and radiotherapy
5. Has completed chemoradiotherapy without progression per RECIST 1.1. (ie, achieved CR, PR, or SD).
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
7. Minimum life expectancy of 12 weeks.
8. Adequate organ function
9. Toxicities attributed to concurrent chemoradiotherapy resolved to grade ≤ 1, unless otherwise specified. Excluding alopecia or fatigue.

Exclusion criteria 26

1. Extensive-stage SCLC
2. Received sequential chemotherapy and thoracic radiotherapy during chemoradiation.
3. Prior therapy with any selective inhibitor of the DLL3 pathway.
4. Prior history of severe or life-threatening events from any immunemediated therapy.
5. Receiving another anti-cancer therapy. Adjuvant hormonal therapy for resected breast cancer is permitted.
6. Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment
7. Major surgical procedures within 28 days prior to first dose of study treatment.
8. Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study treatment. Inactive vaccines and live viral non-replicating vaccines within 3 days prior to first dose of study treatment.
9. Treatment in an alternative investigational trial within 28 days prior to enrollment.
10. Female subjects of childbearing potential unwilling to use protocol specified method of contraception see protocol Appendix 5 (Section 11.5) during treatment and for an additional 60 days after the last dose of study treatment.
11. Female subjects who are breastfeeding or to become pregnant who plan to breastfeed or while on study through 60 days after the last dose of study treatment.
12. Any previous diagnosis of transformed non-small-cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) activating mutation positive NSCLC that has transformed to SCLC, or mixed SCLC NSCLC histology.
13. Female subjects planning to become pregnant or donate eggs while on study through 60 days after the last dose of study treatment.
14. Male subjects with a female partner of childbearing potential or a pregnant partner who are unwilling to practice sexual abstinence or use contraception during treatment and for an additional 60 days after the last dose of study treatment
15. Male subjects unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of study treatment.
16. Subject has known sensitivity to any of the products or components to be administered during dosing.
17. Subject likely to not be available to complete all protocol-required study visits or procedures
18. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
19. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
20. History of other malignancy within the past 2 years. Refer to protocol section 5.2 for more details.
21. History of solid organ transplantation.
22. Myocardial infarction and/or symptomatic congestive heart failure within 6 months prior to first dose of study treatment.
23. History of arterial thrombosis within 6 months prior to first dose of study treatment.
24. Presence of active Human immunodeficiency virus (HIV) or active hepatitis infection. Refer to protocol section 8.4.5.5 for more details.
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. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PFS (BICR)
2. OS

Secondary endpoints 6

1. PFS (investigator)
2. Complete response (CR) based on BICR and investigator assessment per RECIST 1.1. XX based on BICR and investigator assessment per RECIST 1.1. Duration of complete response.
3. "PFS and OS rate at 6 months, 1 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 after randomization
5. Serum concentration of tarlatamab
6. Incidence of anti-tarlatamab antibody formation

Investigational products

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

Test 2

Placebo 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

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 13

Locations

12 EU/EEA countries · 76 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 123 files

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

Application history

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