Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC)
- Conditions
- Small Cell Lung Carcinoma
- Interventions
- Registration Number
- NCT03319940
- Lead Sponsor
- Amgen
- 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 (BiTEĀ®) targeting delta-like protein 3 (DLL3)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 269
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part D CRS Mitigation Strategies Tarlatamab with additional CRS mitigation strategies Part C Pembrolizumab Tarlatamab with Pembrolizumab Part F Tarlatamab Tarlatamab administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only) Part G Tarlatamab Tarlatamab additional dosing schedule Optional wearable digital device substudy (US sites only) Part A Tarlatamab Tarlatamab monotherapy Part C Tarlatamab Tarlatamab with Pembrolizumab Part D Tarlatamab Tarlatamab with additional CRS mitigation strategies Part E Tarlatamab Tarlatamab administration with 24-hour monitoring
- Primary Outcome Measures
Name Time Method Number of participants with dose limiting toxicities (DLT) for all indications 6 months Number of participants with treatment-emergent adverse events (AEs) for all indications 4 years Number of participants with treatment-related AEs for all indications 4 years Number of participants with clinically significant changes in vital signs for all indications 4 years Number of participants with significant changes in electrocardiogram (ECG) for all indications 4 years Number of participants with significant changes in physical examinations for all indications 4 years Number of participants with significant changes in clinical laboratory tests for all indications 4 years
- Secondary Outcome Measures
Name Time Method Maximum observed concentration (Cmax) following intravenous administration for all indications 4 years Minimum observed concentration (Cmin) following intravenous administration for all indications 4 years Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications 4 years Accumulation following multiple dosing for all indications 4 years Half-life (t1/2) following intravenous administration for all indications 4 years Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 4 years Only for parts A, D, E, F, and G
Duration of Response (DOR) for all indications 4 years Time to Response (TTR) 4 years 9-month Progression-Free Survival (PFS) for all indications 9 months 9-month Overall Survival (OS) for all indications 9 months
Trial Locations
- Locations (39)
The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic
šŗšøColumbus, Ohio, United States
University Hospitals Cleveland Medical Center
šŗšøCleveland, Ohio, United States
Landeskrankenhaus Salzburg
š¦š¹Salzburg, Austria
Prince of Wales Hospital
šš°Shatin, New Territories, Hong Kong
Tri-Service General Hospital
šØš³Taipei, Taiwan
Medizinische Universitaet Graz
š¦š¹Graz, Austria
City of Hope National Medical Center
šŗšøDuarte, California, United States
Biokinetica SA
šµš±Jozefow, Poland
Kaohsiung Medical University Chung-Ho Memorial Hospital
šØš³Kaohsiung, Taiwan
Washington University
šŗšøSaint Louis, Missouri, United States
Gustave Roussy
š«š·Villejuif, France
Universitaetsklinikum Wuerzburg
š©šŖWuerzburg, Germany
National Cancer Center Hospital
šÆšµChuo-ku, Tokyo, Japan
Nederlands Kanker Instituut Antoni van Leeuwenhoekziekenhuis
š³š±Amsterdam, Netherlands
Maastricht Universitair Medisch Centrum
š³š±Maastricht, Netherlands
Hospital Clinic i Provincial de Barcelona
šŖšøBarcelona, CataluƱa, Spain
Kantonsspital St Gallen
šØšSankt Gallen, Switzerland
Hospital Universitario 12 de Octubre
šŖšøMadrid, Spain
Hospital Universitario La Paz
šŖšøMadrid, Spain
Winship Cancer Institute
šŗšøAtlanta, Georgia, United States
University of Chicago
šŗšøChicago, Illinois, United States
John Hopkins Sidney Kimmel Comprehensive Cancer Center
šŗšøBaltimore, Maryland, United States
Memorial Sloan Kettering Cancer Center
šŗšøNew York, New York, United States
Fox Chase Cancer Center
šŗšøPhiladelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Cancer Pavillion
šŗšøPittsburgh, Pennsylvania, United States
Chris OBrien Lifehouse
š¦šŗCamperdown, New South Wales, Australia
National Cancer Center Hospital East
šÆšµKashiwa-shi, Chiba, Japan
Wakayama Medical University Hospital
šÆšµWakayama-shi, Wakayama, Japan
Europejskie Centrum Zdrowia Otwock Szpital imienia Fryderyka Chopina
šµš±Otwock, Poland
Hospital Universitari Vall d Hebron
šŖšøBarcelona, CataluƱa, Spain
Hospital Universitario Ramon y Cajal
šŖšøMadrid, Spain
Centre Hospitalier Universitaire Vaudois
šØšLausanne, Switzerland
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
šØš³Taoyuan, Taiwan
Christie Hospital
š¬š§Manchester, United Kingdom
Ochsner Clinic Foundation
šŗšøNew Orleans, Louisiana, United States
Yale New Haven Hospital
šŗšøNew Haven, Connecticut, United States
Moffitt Cancer Center
šŗšøTampa, Florida, United States
Henry Ford Health System
šŗšøDetroit, Michigan, United States
Sarah Cannon Research Institute
šŗšøNashville, Tennessee, United States