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 (BiTE®) 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
🇺🇸Columbus, Ohio, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Landeskrankenhaus Salzburg
🇦🇹Salzburg, Austria
Prince of Wales Hospital
🇭🇰Shatin, New Territories, Hong Kong
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Medizinische Universitaet Graz
🇦🇹Graz, Austria
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Biokinetica SA
🇵🇱Jozefow, Poland
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Washington University
🇺🇸Saint Louis, Missouri, United States
Gustave Roussy
🇫🇷Villejuif, France
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Nederlands Kanker Instituut Antoni van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Maastricht Universitair Medisch Centrum
🇳🇱Maastricht, Netherlands
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Cataluña, Spain
Kantonsspital St Gallen
🇨🇭Sankt Gallen, Switzerland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
John Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Cancer Pavillion
🇺🇸Pittsburgh, Pennsylvania, United States
Chris OBrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama-shi, Wakayama, Japan
Europejskie Centrum Zdrowia Otwock Szpital imienia Fryderyka Chopina
🇵🇱Otwock, Poland
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Cataluña, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
🇨🇳Taoyuan, Taiwan
Christie Hospital
🇬🇧Manchester, United Kingdom
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States