A Phase 2 Study of Tarlatamab in Patients With Small Cell Lung Cancer (SCLC) (DeLLphi-301)

• ClinicalTrials.gov Identifier: NCT05060016
• Recruitment Status: Active, not recruiting
• First Posted: September 28, 2021
• Last Update Posted: May 13, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: September 17, 2021
• First Posted Date: September 28, 2021
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: December 1, 2021
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2023)

• Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Part 1 and Part 3 Only: Number of Participants who Experience One or More Treatment-emergent Adverse Events [ Time Frame: Up to a maximum of 24 months ]
• Part 1 Only: Serum Concentrations of Tarlatamab [ Time Frame: Up to a maximum of 24 months ]
• Part 1 and Part 2 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]

Original Primary Outcome Measures (submitted: September 17, 2021)

• Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Part 1 Only: Number of Participants who Experience One or More Treatment-emergent Adverse Events [ Time Frame: Up to a maximum of 24 months ]
• Part 1 Only: Serum Concentrations of AMG 757 [ Time Frame: Up to a maximum of 24 months ]
• Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]

Current Secondary Outcome Measures (submitted: February 3, 2022)

• Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Progression-free Survival (PFS) Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Overall Survival (OS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Number of Participants who Experience One or More Treatment-emergent Adverse Events [ Time Frame: Up to a maximum of 24 months ]
• Serum Concentrations of Tarlatamab [ Time Frame: Up to a maximum of 24 months ]
• Number of Participants who Experience Anti-Tarlatamab Antibody Formation [ Time Frame: Up to a maximum of 24 months ]

Original Secondary Outcome Measures (submitted: September 17, 2021)

• Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Progression-free Survival (PFS) Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to a maximum of 24 months ]
• Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Overall Survival (OS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator [ Time Frame: Up to a maximum of 24 months ]
• Number of Participants who Experience One or More Treatment-emergent Adverse Events [ Time Frame: Up to a maximum of 24 months ]
• Serum Concentrations of AMG 757 [ Time Frame: Up to a maximum of 24 months ]
• Number of Participants who Experience Anti-AMG 757 Antibody Formation [ Time Frame: Up to a maximum of 24 months ]

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

Descriptive Information

• Brief Title: A Phase 2 Study of Tarlatamab in Patients With Small Cell Lung Cancer (SCLC)
• Official Title: A Phase 2 Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of Tarlatamab in Subjects With Relapsed/Refractory Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-301).

Brief Summary

The main aim of this study is to:

• evaluate safety and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1] by investigator) of 2 dose levels of tarlatamab for Part 1 only
• evaluate anti-tumor activity of tarlatamab as determined by objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) for Part 1 and 2
• evaluate safety of reduced mandatory monitoring period in Cycle 1 at selected dose of tarlatamab for Part 3

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Relapsed/Refractory Small Cell Lung Cancer

Intervention

Drug: Tarlatamab

Intravenous (IV) infusion

Study Arms

• Experimental: Part 1: Tarlatamab Low Dose
  Participants will receive the low dose of Tarlatamab.
  Intervention: Drug: Tarlatamab
• Experimental: Part 1: Tarlatamab High Dose
  Participants will receive the high dose of Tarlatamab.
  Intervention: Drug: Tarlatamab
• Experimental: Part 2: Dose Expansion
  Participants will receive the selected target dose of Tarlatamab based on findings in Part 1.
  Intervention: Drug: Tarlatamab
• Experimental: Part 3: Modified Monitoring Substudy
  Participants will receive the selected target dose of Tarlatamab based on findings in Part 1 with reduced Cycle 1 monitoring requirements.
  Intervention: Drug: Tarlatamab

• Publications *: Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Epub 2023 Oct 20.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 30, 2023): 222
• Original Estimated Enrollment (submitted: September 17, 2021): 160
• Estimated Study Completion Date: October 31, 2025
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
• Male and female participants ≥ 18 years of age (or legal adult age within country) at the time of signing the informed consent.
• Histologically or cytologically confirmed relapsed/refractory SCLC
• Participants who progressed or recurred following 1 platinum-based regimen and at least 1 other prior line of therapy.
• Participants willing to provide archived tumor tissue samples or willing to undergo pretreatment tumor biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 1.
• Minimum life expectancy of 12 weeks.
• Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first dose of tarlatamab.
• Participants with treated brain metastases are eligible provided they meet defined criteria.

Exclusion Criteria:

Disease Related

• Untreated or symptomatic brain metastases and leptomeningeal disease.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Participants who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
• Unresolved toxicity from prior anti-tumor therapy, defined as per protocol.

Other Medical Conditions

• History of other malignancy within the past 2 years, with exceptions
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of tarlatamab.
• History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of tarlatamab.
• 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 tarlatamab.
• Presence of any indwelling line or drain.
• History of hypophysitis or pituitary dysfunction.
• Exclusion of hepatitis infection based on the results and/or criteria per protocol.
• Major surgery within 28 days of first dose of tarlatamab.
• History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Subject is eligible if no acute symptoms of coronavirus disease 2019 (COVID-19) within 14 days prior to first dose of tarlatamab (counted from day of positive test for asymptomatic subjects).

Prior/Concomitant Therapy

• Participant received prior therapy with tarlatamab.
• Prior anti-cancer therapy within 28 days prior to first dose of tarlatamab.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of tarlatamab.

• The following vaccines (live and live-attenuated vaccines) are excluded during the following study periods:

  1. Screening and during study treatment: Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of tarlatamab and for the duration of the study. Live viral non-replicating vaccine (e.g. Jynneos) for Monkeypox infection is allowed during the study (except during cycle 1) in accordance with local standard of care and institutional guidelines.
  2. End of study treatment: Live and live-attenuated vaccines can be used when at least 42 days (5X half-life of tarlatamab) have passed after the last dose of tarlatamab.

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 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 and/or day 1 by a highly sensitive urine or 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.
• Participant has known sensitivity 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.

Specific Exclusions to Part 3

• Participants unable to remain within one hour of study site for 48 hours after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.
• Participants unable to remain within one hour of any hospital for 72 hours after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.
• Unable to identify home companion who will cohabitate with participant for 72 hours after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Denmark, France, Germany, Greece, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05060016
• Other Study ID Numbers: 20200491; 2021-002566-40 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

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