Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer (DeLLphi-304)

• ClinicalTrials.gov Identifier: NCT05740566
• Recruitment Status: Recruiting
• First Posted: February 23, 2023
• Last Update Posted: May 16, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: February 7, 2023
• First Posted Date: February 23, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: May 31, 2023
• Estimated Primary Completion Date: August 1, 2027 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 19, 2024): Overall Survival (OS) [ Time Frame: Up to approximately 4 years ]
• Original Primary Outcome Measures (submitted: February 21, 2023): Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]

Current Secondary Outcome Measures (submitted: February 19, 2024)

• Progression Free Survival (PFS) [ Time Frame: Up to approximately 4 years ]
• Change from Baseline In Selected Functional Scales and Disease Symptom Items Included in Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Up to approximately 4 years ]
• Change from Baseline in Selected Disease Symptoms Included in Lung Cancer Quality of Life Questionnaire (EORTC-QLQ-LC13) [ Time Frame: Up to approximately 4 years ]
• Overall Response (OR) [ Time Frame: Up to approximately 4 years ]
• Disease Control (DC) [ Time Frame: Up to approximately 4 years ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 4 years ]
• PFS [ Time Frame: 1 year ]
• OS [ Time Frame: 1 year, 2 years and 3 years ]
• Incidence of Treatment-Emergent Adverse Events (TEAE) [ Time Frame: Up to approximately 4 years ]
• Serum Concentrations of Tarlatamab [ Time Frame: Up to 1 year ]
• Number of Participants Who Experience Anti-tarlatamab Antibodies [ Time Frame: Up to 1 year ]
• Change from Baseline in Pain Severity as Measured by Brief Pain Inventory - Short Form (BPI-SF) [ Time Frame: Up to approximately 4 years ]
• Patient Perceived Health at Each Assessment Visit Using Visual Analogue Scale (VAS) [ Time Frame: Up to approximately 4 years ]
• Change from Baseline in Patient Perceived Health Using Visual Analog Scale (VAS) [ Time Frame: Up to approximately 4 years ]
• Responses to Patient-Reported Adverse Events Questionnaire (PRO-CTCAE) [ Time Frame: Up to approximately 4 years ]
• Change from Baseline in Symptom Severity as Measured by Patient Global Impression of Severity (PGIS) Questionnaire [ Time Frame: Up to approximately 4 years ]
• Change from Baseline in Symptoms and Overall Status as Measured by Patient Reported Impression of Change (PGIC) Questionnaire [ Time Frame: Up to approximately 4 years ]
• Change from Baseline in Symptom Bother as Measured by Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire [ Time Frame: Up to approximately 4 years ]

Original Secondary Outcome Measures (submitted: February 21, 2023)

• Progression Free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
• Change from Baseline In Selected Functional Scales and Disease Symptom Items Included in Cancer Quality of Life Questionnaire [ Time Frame: Up to approximately 5 years ]
• Change from Baseline in Selected Disease Symptoms Included in Lung Cancer Quality of Life Questionnaire [ Time Frame: Up to approximately 5 years ]
• Overall Response (OR) [ Time Frame: Up to approximately 5 years ]
• Disease Control (DC) [ Time Frame: Up to approximately 5 years ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 5 years ]
• PFS [ Time Frame: 1 year ]
• OS [ Time Frame: 1 year, 2 years and 3 years ]
• Incidence of Treatment-Emergent Adverse Events (TEAE) [ Time Frame: Up to approximately 5 years ]
• Serum Concentrations of Tarlatamab [ Time Frame: Up to 1 year ]
• Number of Participants Who Experience Anti-tarlatamab Antibodies [ Time Frame: Up to 1 year ]
• Change from Baseline in Pain Questionnaire [ Time Frame: Up to approximately 6 months ]
• Patient Perceived Health at Each Assessment Visit Using Visual Analogue Scale (VAS) [ Time Frame: Up to approximately 5 years ]
• Change from Baseline in Patient Perceived Health Using VAS [ Time Frame: Up to approximately 5 years ]
• Responses to Patient-Reported Adverse Events Questionnaire [ Time Frame: Up to approximately 5 years ]
• Change from Baseline in Patient Reported Symptom Severity [ Time Frame: Up to approximately 5 years ]
• Change from Baseline of Overall Symptoms and Status in Patient Reported Impression of Change Questionnaire [ Time Frame: Up to approximately 5 years ]
• Change from Baseline in Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire [ Time Frame: Up to approximately 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer
• Official Title: A Randomized, Open-label, Phase 3 Study of Tarlatamab Compared With Standard of Care in Subjects With Relapsed Small Cell Lung Cancer After Platinum-based First-line Chemotherapy
• Brief Summary: The main objective is to compare the efficacy of tarlatamab with standard of care (SOC) on prolonging overall survival (OS).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer (SCLC)

Intervention

• Drug: Tarlatamab
  Tarlatamab will be administered as an IV infusion.
  Other Name: AMG 757
• Drug: Lurbinectedin
  Lurbinectedin will be administered per local SOC.
• Drug: Topotecan
  Topotecan will be administered per local SOC.
• Drug: Amrubicin
  Amrubicin will be administered per local SOC.

Study Arms

• Experimental: Tarlatamab
  Participants will receive tarlatamab as an intravenous (IV) infusion.
  Intervention: Drug: Tarlatamab
• Active Comparator: Standard of Care
  Participants will receive treatment per local standard of care (SOC).
  Interventions:

  • Drug: Lurbinectedin
  • Drug: Topotecan
  • Drug: Amrubicin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 19, 2024): 490
• Original Estimated Enrollment (submitted: February 21, 2023): 700
• Estimated Study Completion Date: August 1, 2027
• Estimated Primary Completion Date: August 1, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥ 18 years (or legal adult age within country, whichever is older) at the time of signing the informed consent.
• Histologically or cytologically confirmed SCLC with demonstrated progression or relapse.
• Participants who progressed or recurred following 1 platinum-based regimen.
• Measurable disease as defined per RECIST 1.1 within the 21-day screening period.
• Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
• Minimum life expectancy of 12 weeks.
• Adequate organ function.

Exclusion Criteria:

• Disease Related

  • Symptomatic central nervous system (CNS) metastases with exceptions defined in the protocol.
  • Diagnosis or evidence of leptomeningeal disease.
  • Prior history of immune checkpoint inhibitors resulting in events defined in the protocol.

• Other Medical Conditions

  • Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy.
  • History of solid organ transplantation.
  • History of other malignancy within the past 2 years, with exceptions defined in the protocol.
  • Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months prior to first dose of study treatment.
  • History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months prior to first dose of study treatment.
  • Presence or history of viral infection based on criteria per protocol.
  • Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to first dose of study treatment.
  • Symptoms and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection requiring antibiotics within 7 days prior to the first dose study treatment.
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.

• Prior/Concomitant Therapy

  • Prior therapy with tarlatamab or any of the standard of care chemotherapy included as part of this trial or participation in any tarlatamab or any other DLL3 targeted agent clinical trial.
  • Prior therapy with any selective inhibitor of the DLL3 pathway.
  • Participant received more than one prior systemic therapy regimen for SCLC.
  • Prior anti-cancer therapy within 21 days prior to first dose of study treatment with exceptions defined in protocol.
  • Current anti-cancer therapy such as chemotherapy, immunotherapy, or targeted therapy with exceptions.
  • Use of herbal or prescription/non-prescription medications known to inhibit membrane transporters P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) within 7 days prior to the first dose of study treatment.
  • Use of herbal or prescription/non-prescription medications known to be moderate or strong inhibitors of cytochrome P450 3A (CYP3A) enzymes within 7 days prior to the first dose of study treatment.
  • Use of herbal or prescription/non-prescription medications known to be moderate or strong inducers of CYP3A enzymes within 28 days prior to first dose of study treatment.
  • Participants who have reached the limit dose of prior treatment with cardiotoxic drugs.
  • Major surgical procedures within 28 days prior to first dose of study treatment.
  • Live and live-attenuated vaccines within 14 days prior to the start of study treatment.
  • Inactive vaccines and live viral non-replicating vaccines within 3 days prior to the first dose of study treatment.
  • Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

• Diagnostic Assessments

  • 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, with exceptions defined in the protocol.

• Other Exclusions

  • Female participants of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 72 days after the last dose of tarlatamab.
  • Female participants who are breastfeeding or who plan to breastfeed while on study through 72 days after the last dose of tarlatamab.
  • Female participants planning to become pregnant or donate eggs while on study through 72 days after the last dose of tarlatamab.
  • Female participants of childbearing potential with a positive pregnancy test assessed at screening by a 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 and for an additional 132 days after the last dose of tarlatamab.
  • Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 132 days after the last dose of tarlatamab.
  • Male participants unwilling to abstain from donating sperm during treatment and for an additional 132 days after the last dose of tarlatamab.
  • Contraception requirements for male and female participants receiving SOC therapies are based on regional prescribing information.
  • Breastfeeding restrictions for female participants receiving SOC therapies are based on regional prescribing information.
  • Participant has known sensitivity or is contraindicated to any of the products or components to be administered during dosing.
  • Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures.
  • History or evidence of any other clinically significant disorder, condition or disease determined by the investigator or Amgen physician that would pose a risk to the subject safety or interfere with the study evaluation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amgen Call Center; 866-572-6436; medinfo@amgen.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05740566
• Other Study ID Numbers: 20210004
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: May 2024