Study Comparing Tarlatamab and Durvalumab Versus Durvalumab Alone in First-Line Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following Platinum, Etoposide and Durvalumab (DeLLphi-305)

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Small-Cell Lung Cancer; Extensive-Stage Small-Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Tarlatamab

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tarlatamab in Combination With Durvalumab; Participants will receive tarlatamab once every 2 weeks (Q2W) and durvalumab once every 4 weeks (Q4W).	Drug: Durvalumab; IV infusion; Drug: Tarlatamab; Intravenous (IV) infusion; Other Names: AMG 757
Active Comparator: Durvalumab Alone; Participants will receive durvalumab Q4W alone.	Drug: Durvalumab; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
OS	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
OS at 2 Years	2 years
Progression Free Survival (PFS)	Up to approximately 3 years
Overall Response (OR)	Up to approximately 3 years
Disease Control (DC) Rate	Up to approximately 3 years
Duration of Response (DoR)	Up to approximately 3 years
PFS at 6 Months	6 months
PFS at 1 Year	1 year
PFS at 2 Years	2 years
OS at 6 Months	6 months
OS at 1 Year	1 year
OS at 3 Years	3 years
Time to Progression (TTP)	Up to approximately 3 years
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Up to approximately 9 months
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
Number of Participants with Serious TEAEs	Up to approximately 3 years
Number of Participants with TEAEs Leading to Discontinuation of Treatment	Up to approximately 3 years
Number of Participants with Fatal TEAEs	Up to approximately 3 years
Number of Participants with Treatment-related Adverse Events (AEs)	Up to approximately 9 months
Number of Participants with Adverse Events of Interest (EOI)	Up to approximately 9 months
Serum Concentrations of Tarlatamab	Day 1 up to approximately 6 months
Number of Participants with Antitarlatamab Antibody Formation	Up to approximately 9 months
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
Change in Disease Symptoms of Cough as Measured Using EORTC-QLQ LC13	Up to 12 months
Change in Disease Symptoms of Chest Pain as Measured Using EORTC-QLQ LC13	Up to 12 months
Change in Disease Symptoms of Dyspnea as Measured Using EORTC-QLQ LC13	Up to 12 months
TTD for Global Health Status as Measured by EORTC-QLQ-C30	Up to approximately 9 months
TTD for Quality of Life as Measured by EORTC-QLQ-C30	Up to approximately 9 months

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Estimated): June 12, 2024
• Primary Completion (Estimated): September 12, 2027
• Study Completion (Estimated): September 25, 2028

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Platinum; Etoposide; Durvalumab; ES-SCLC; AMG 757; Tarlatamab; Extensive-Stage Small-Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; AMG 757
• Other Study ID Numbers: 20200041; 2023-505989-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No