Study Comparing Tarlatamab and Durvalumab Versus Durvalumab Alone in First-Line Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following Platinum, Etoposide and Durvalumab

Small-Cell Lung Cancer Clinical Trial

— DeLLphi-305  

Official title:

A Phase 3, Open-label, Multicenter, Randomized Study of Tarlatamab in Combination With Durvalumab vs Durvalumab Alone in Subjects With Extensive-Stage Small-Cell Lung Cancer Following Platinum, Etoposide and Durvalumab (DeLLphi-305)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06211036
• Other study ID #: 20200041
• Secondary ID: 2023-505989-29
• Status: Recruiting
• Phase: Phase 3
• Start date: June 5, 2024
• Est. completion date: September 25, 2028

Study information

• Verified date: June 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the efficacy of tarlatamab plus durvalumab with durvalumab alone on prolonging overall survival (OS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: September 25, 2028
• Est. primary completion date: September 5, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.

• Age >= 18 years (or >= legal adult age within the country if it is older than 18 years).

• Histologically or cytologically documented extensive-stage disease (American Joint Committee on Cancer, 2017, IV small-cell lung cancer (SCLC) [T any, N any, M1 a/b]), 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.

• Completed 3-4 cycles of platinum-etoposide chemotherapy with concurrent durvalumab as first-line treatment of extensive-stage (ES)-SCLC prior to enrollment, without disease progression (ongoing response or stable disease) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.

• Minimum life expectancy > 12 weeks.

• Toxicities attributed to prior anti-cancer therapy resolved to grade = 1, unless otherwise specified, excluding alopecia or fatigue.

• Adequate organ function

Exclusion

• Symptomatic central nervous system (CNS) metastases, or leptomeningeal disease. Participants with treated brain metastases are eligible as per protocol

• Prior history of severe or life-threatening events from any immune-mediated therapy. • History of other malignancy withing the past 2 years, with some exceptions as per protocol.

• Active or prior documented autoimmune or inflammatory disorders as per protocol

• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months of first dose of study treatment.

• History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months of first dose of study treatment.

• Evidence of interstitial lung disease (ILD) or active, non-infectious pneumonitis.

• History of solid organ transplant.

• Major surgical procedures within 28 days of first dose of study treatment.

• Known human immunodeficiency virus (HIV) infection (participants with HIV infection on antiviral therapy and undetectable viral load are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on study), hepatitis C infection (participants with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (participants with hepatitis B surface antigen [HBsAg] or core antibody that achieve sustained virologic response with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study).

• Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment:

• History of allergic reactions or acute hypersensitivity reaction to antibody therapies, platinum chemotherapy, or etoposide.

• Participant 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.

• Participant has known active infection requiring parenteral antibiotic treatment. Upon completion of parenteral antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint.

• Treatment with live virus, including live-attenuated vaccination, within 4 weeks prior to the first dose of study treatment. Inactive vaccines (e.g., non-live or non-replicating agent) and live viral non-replicating vaccines (e.g., Jynneos for Monkeypox infection) within 30 days prior to first dose of study treatment.

• Prior therapy with any selective inhibitor of the delta-like ligand 3 (DLL3) pathway.

• Receiving another anti-cancer therapy. Adjuvant hormonal therapy for resected breast cancer is permitted.

• Treatment in an alternative investigational trial within 28 days prior to enrollment.

• Has received or is planning to receive consolidative chest radiation for extensive stage disease.

• Female participants of childbearing potential unwilling to use protocol specified method of contraception during treatment as per protocol

• Female participants who are breastfeeding or who plan to breastfeed while on study as per protocol

• Female participants planning to become pregnant or donate eggs while on study as per protocol

• Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test.

• Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment as per protocol

• Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment as per protocol

• Male participants unwilling to abstain from donating sperm during treatment as per protocol

• Participant has known sensitivity to any of the products or components to be administered during dosing.

• Participant has known sensitivity to any of the products or components to be administered during dosing.

• Participant likely not to be available to complete all protocol-required study visits or procedures to the best of the participant and investigator's knowledge.

• History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or physician if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.

Related Conditions & MeSH terms

• Extensive-Stage Small-Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma
• Small-Cell Lung Cancer

Intervention

Drug:
• Tarlatamab
Intravenous (IV) infusion
• Durvalumab
IV infusion

Locations

Country	Name	City	State
China	Jilin Cancer Hospital	Changchun	Jilin
Japan	Kurume University Hospital	Kurume-shi	Fukuoka
Switzerland	Universitaetsspital Basel	Basel
Turkey	Medical Park Seyhan Hastanesi	Mersin
Turkey	VM Medical Park Mersin Hastanesi	Mersin
United States	Our Lady of the Lake Cancer Institute	Baton Rouge	Louisiana
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Baptist Cancer Center Memphis Thoracic	Memphis	Tennessee
United States	Nebraska Cancer Specialists	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  China,  Japan,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OS		Up to approximately 3 years
Secondary	Progression Free Survival (PFS)		Up to approximately 3 years
Secondary	Overall Response (OR)		Up to approximately 3 years
Secondary	Disease Control (DC) Rate		Up to approximately 3 years
Secondary	Duration of Response (DoR)		Up to approximately 3 years
Secondary	PFS at 6 Months		6 months
Secondary	PFS at 1 Year		1 year
Secondary	PFS at 2 Years		2 years
Secondary	OS at 6 Months		6 months
Secondary	OS at 1 Year		1 year
Secondary	OS at 2 Years		2 years
Secondary	OS at 3 Years		3 years
Secondary	Time to Progression (TTP)		Up to approximately 3 years
Secondary	Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Up to approximately 9 months
Secondary	Number of Participants with TEAEs Grade 3 or Above per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.		Up to approximately 3 years
Secondary	Number of Participants with Serious TEAEs		Up to approximately 3 years
Secondary	Number of Participants with TEAEs Leading to Discontinuation of Treatment		Up to approximately 3 years
Secondary	Number of Participants with Fatal TEAEs		Up to approximately 3 years
Secondary	Number of Participants with Treatment-related Adverse Events (AEs)		Up to approximately 9 months
Secondary	Number of Participants with Adverse Events of Interest (EOI)		Up to approximately 9 months
Secondary	Serum Concentrations of Tarlatamab		Day 1 up to approximately 6 months
Secondary	Number of Participants with Antitarlatamab Antibody Formation		Up to approximately 9 months
Secondary	Time to First Deterioration (TTD) for Physical Function as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30)		Up to approximately 9 months
Secondary	Change in Disease Symptoms of Cough as Measured Using EORTC-QLQ LC13		Up to 12 months
Secondary	Change in Disease Symptoms of Chest Pain as Measured Using EORTC-QLQ LC13		Up to 12 months
Secondary	Change in Disease Symptoms of Dyspnea as Measured Using EORTC-QLQ LC13		Up to 12 months
Secondary	TTD for Global Health Status as Measured by EORTC-QLQ-C30		Up to approximately 9 months
Secondary	TTD for Quality of Life as Measured by EORTC-QLQ-C30		Up to approximately 9 months

External Links

•   AmgenTrials clinical trials website