Clinical trial NCT03319940: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Small Cell Lung Carcinoma
Keywords: Half-Life Extended (HLE) Bispecific T cell engager (BiTE®)
Delta-like protein 3 (DLL3)
Tarlatamab
Oncology
Immunology
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-10-24
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLT) for all indications
timeFrame: 6 months
measure: Number of participants with treatment-emergent adverse events (AEs) for all indications
timeFrame: 4 years
measure: Number of participants with treatment-related AEs for all indications
timeFrame: 4 years
measure: Number of participants with clinically significant changes in vital signs for all indications
timeFrame: 4 years
measure: Number of participants with significant changes in electrocardiogram (ECG) for all indications
timeFrame: 4 years
measure: Number of participants with significant changes in physical examinations for all indications
timeFrame: 4 years
measure: Number of participants with significant changes in clinical laboratory tests for all indications
timeFrame: 4 years
Secondary outcomes:
measure: Maximum observed concentration (Cmax) following intravenous administration for all indications
timeFrame: 4 years
measure: Minimum observed concentration (Cmin) following intravenous administration for all indications
timeFrame: 4 years
measure: Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications
timeFrame: 4 years
measure: Accumulation following multiple dosing for all indications
timeFrame: 4 years
measure: Half-life (t1/2) following intravenous administration for all indications
timeFrame: 4 years
measure: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: 4 years
measure: Duration of Response (DOR) for all indications
timeFrame: 4 years
measure: Time to Response (TTR)
timeFrame: 4 years
measure: 9-month Progression-Free Survival (PFS) for all indications
timeFrame: 9 months
measure: 9-month Overall Survival (OS) for all indications
timeFrame: 9 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Cancer Pavillion
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Villejuif
country: France
facility: Gustave Roussy
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut Antoni van Leeuwenhoekziekenhuis
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Jozefow
country: Poland
facility: Biokinetica SA
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital imienia Fryderyka Chopina
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Sankt Gallen
country: Switzerland
facility: Kantonsspital St Gallen
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
city: Manchester
country: United Kingdom
facility: Christie Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Dowlati A, Hummel HD, Champiat S, Olmedo ME, Boyer M, He K, Steeghs N, Izumi H, Johnson ML, Yoshida T, Bouchaab H, Borghaei H, Felip E, Jost PJ, Gadgeel S, Chen X, Yu Y, Martinez P, Parkes A, Paz-Ares L. Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update. J Clin Oncol. 2024 Oct 10;42(29):3392-3399. doi: 10.1200/JCO.24.00553. Epub 2024 Aug 29.
citation: 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.