Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC)

• ClinicalTrials.gov Identifier: NCT03319940
• Recruitment Status: Recruiting
• First Posted: October 24, 2017
• Last Update Posted: April 11, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: October 5, 2017
• First Posted Date: October 24, 2017
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: December 26, 2017
• Estimated Primary Completion Date: October 22, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2023)

• Number of participants with dose limiting toxicities (DLT) for all indications [ Time Frame: 6 months ]
• Number of participants with treatment-emergent adverse events (AEs) for all indications [ Time Frame: 4 years ]
• Number of participants with treatment-related AEs for all indications [ Time Frame: 4 years ]
• Number of participants with clinically significant changes in vital signs for all indications [ Time Frame: 4 years ]
• Number of participants with significant changes in electrocardiogram (ECG) for all indications [ Time Frame: 4 years ]
• Number of participants with significant changes in physical examinations for all indications [ Time Frame: 4 years ]
• Number of participants with significant changes in clinical laboratory tests for all indications [ Time Frame: 4 years ]

Original Primary Outcome Measures (submitted: October 19, 2017)

• Subject incidence of dose limiting toxicity [ Time Frame: 3 years ]
  Number of subjects who experience dose limiting toxicities
• Subject incidence of treatment-emergent and treatment-related adverse events [ Time Frame: 3 years ]
  Number of subjects who experience treatment-emergent and treatment-related adverse events

Current Secondary Outcome Measures (submitted: June 14, 2023)

• Maximum observed concentration (Cmax) following intravenous administration for all indications [ Time Frame: 4 years ]
• Minimum observed concentration (Cmin) following intravenous administration for all indications [ Time Frame: 4 years ]
• Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications [ Time Frame: 4 years ]
• Accumulation following multiple dosing for all indications [ Time Frame: 4 years ]
• Half-life (t1/2) following intravenous administration for all indications [ Time Frame: 4 years ]
• Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: 4 years ]
  Only for parts A, D, E, F, and G
• Duration of Response (DOR) for all indications [ Time Frame: 4 years ]
• Time to Response (TTR) [ Time Frame: 4 years ]
• 9-month Progression-Free Survival (PFS) for all indications [ Time Frame: 9 months ]
• 9-month Overall Survival (OS) for all indications [ Time Frame: 9 months ]

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

Descriptive Information

• Brief Title: Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC)
• Official Title: A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Tarlatamab in Subjects With Small Cell Lung Cancer (DeLLphi-300)
• Brief Summary: A study to assess the safety, tolerability, and PK of tarlatamab in participants with SCLC
• Detailed Description: This is an open-label, ascending, multiple doses, phase 1 study evaluating tarlatamab monotherapy, in combination with anti-PD1 therapy and with additional cytokine release syndrome (CRS) mitigation strategies. Tarlatamab will be administered as a short term intravenous (IV) infusion in participants with SCLC. Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is an open-label, ascending, multiple doses, phase 1 study evaluating tarlatamab monotherapy, in combination with anti-PD1 therapy and with additional CRS mitigation strategies in participants with SCLC. The dose exploration phases of the study will estimate the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of tarlatamab either as monotherapy or in combination with pembrolizumab. This will be followed by dose expansion phase to confirm RP2D and to obtain further safety and efficacy data.

Masking: None (Open Label)
Masking Description:

The patient, investigator, investigative staff, medical monitor and care provider will not be masked for the study.

Primary Purpose: Treatment

• Condition: Small Cell Lung Carcinoma

Intervention

• Drug: Tarlatamab
  Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
• Drug: Pembrolizumab
  Pembrolizumab is a potent humanized IgG4 monoclonal antibody (mAb) with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and PD-L2
• Drug: CRS Mitigation Strategies
  Participants will be treated with one of the CRS mitigation strategies.

Study Arms

• Experimental: Part A
  Tarlatamab monotherapy
  Intervention: Drug: Tarlatamab
• Experimental: Part C
  Tarlatamab with Pembrolizumab
  Interventions:

  • Drug: Tarlatamab
  • Drug: Pembrolizumab
• Experimental: Part D
  Tarlatamab with additional CRS mitigation strategies
  Interventions:

  • Drug: Tarlatamab
  • Drug: CRS Mitigation Strategies
• Experimental: Part E
  Tarlatamab administration with 24-hour monitoring
  Intervention: Drug: Tarlatamab
• Experimental: Part F

  Tarlatamab administered in outpatient infusion centers with 8-hour monitoring

  Optional wearable digital device substudy (US sites only)

  Intervention: Drug: Tarlatamab
• Experimental: Part G

  Tarlatamab additional dosing schedule

  Optional wearable digital device substudy (US sites only)

  Intervention: Drug: Tarlatamab

Publications *

• Owen DH, Giffin MJ, Bailis JM, Smit MD, Carbone DP, He K. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019 Jun 18;12(1):61. doi: 10.1186/s13045-019-0745-2.
• Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, Hummel HD, Borghaei H, Johnson ML, Steeghs N, Blackhall F, Dowlati A, Reguart N, Yoshida T, He K, Gadgeel SM, Felip E, Zhang Y, Pati A, Minocha M, Mukherjee S, Goldrick A, Nagorsen D, Hashemi Sadraei N, Owonikoko TK. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. J Clin Oncol. 2023 Jun 1;41(16):2893-2903. doi: 10.1200/JCO.22.02823. Epub 2023 Jan 23.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 14, 2023): 392
• Original Estimated Enrollment (submitted: October 19, 2017): 92
• Estimated Study Completion Date: October 21, 2025
• Estimated Primary Completion Date: October 22, 2024 (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 greater than or equal to 18 years old at the time of signing the informed consent
• Histologically or cytologically confirmed SCLC. For parts A, C, D, E, F, and G: relapsed/refractory small cell lung cancer (R/R SCLC) who progressed or recurred following platinum-based regimen
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Participants with treated brain metastases are eligible provided they meet defined criteria
• Adequate organ function as defined in protocol

Exclusion Criteria:

• History of other malignancy within the past 2 years prior to first dose of tarlatamab with exceptions
• Major surgery within 28 days of first dose tarlatamab
• Untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease (regardless of symptomatic or not).
• Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of tarlatamab with the following exceptions: participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade less than or equal to 1; and prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
• Participants who experienced severe, life-threatening or recurrent (Grade 2 or higher) immune-mediated AEs or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immune-oncology agents
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis
• 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
• Part C only: history of solid organ transplantation or active autoimmune disease that has required systemic treatment within the past 2 years
• 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 investigational product administration

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: Australia, Austria, France, Germany, Hong Kong, Japan, Netherlands, Poland, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03319940
• Other Study ID Numbers: 20160323
• Has Data Monitoring Committee: No

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: https://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: April 2024