A Phase 1 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Tarlatamab in Subjects With Small Cell Lung Cancer (DeLLphi-300)
Phase 1
Active, not recruiting
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- 2023-506541-39-00
- Lead Sponsor
- Amgen Inc.
- 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
- Ongoing, recruitment ended
- Sex
- All
- Target Recruitment
- 110
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
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 (11)
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
🇳🇱Amsterdam, Netherlands
Medical University Of Graz
🇦🇹Graz, Austria
Institut Gustave Roussy
🇫🇷Villejuif, France
Europejskie Centrum Zdrowia Otwock Sp. z o.o.
🇵🇱Otwock, Poland
Biokinetica S.A.
🇵🇱Jozefow, Poland
Universitaetsklinikum Wuerzburg AöR
🇩🇪Wuerzburg, Germany
Hospital Universitari Vall D Hebron
🇪🇸Barcelona, Spain
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Scroll for more (1 remaining)Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting🇳🇱Amsterdam, NetherlandsNeeltje SteeghsSite contact+31205129111n.steeghs@nki.nl