Study Evaluating Safety, Tolerability and PK of AMG 757 in Adults With Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
A study to assess the safety, tolerability, and pharmacokinetics of AMG 757 in Subjects with Small Cell Lung Cancer
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
This is an open-label, ascending, multiple dose, phase 1 study evaluating AMG 757 monotherapy, in combination with anti-PD1 therapy and with additional cytokine release syndrome (CRS) mitigation strategies. AMG 757 will be administered as a short term intravenous (IV) infusion in subjects with small cell lung cancer. AMG 757 is a Half Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Part A AMG 757 Monotherapy |
Drug: AMG 757
AMG 757 is a Half Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
|
Experimental: Part C AMG 757 with Pembrolizumab |
Drug: AMG 757
AMG 757 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
|
Experimental: Part D AMG 757 with additional cytokine release syndrome (CRS) mitigation strategies |
Drug: AMG 757
AMG 757 is a Half Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
Drug: CRS Mitigation Strategies
Subjects will be treated with one of the CRS mitigation strategies.
|
Experimental: Part E AMG 757 administration with 24-hour monitoring |
Drug: AMG 757
AMG 757 is a Half Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
|
Experimental: Part F AMG 757 administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only) |
Drug: AMG 757
AMG 757 is a Half Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
|
Experimental: Part G AMG 757 additional dosing schedule Optional wearable digital device substudy (US sites only) |
Drug: AMG 757
AMG 757 is a Half Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
|
Outcome Measures
Primary Outcome Measures
- 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 [24 months]
- Number of participants with treatment-related AEs for all indications [24 months]
- Number of participants with clinically significant changes in vital signs for all indications [24 months]
- Number of participants with significant changes in ECG for all indications [24 months]
- Number of participants with significant changes in physical examinations for all indications [24 months]
- Number of participants with significant changes in clinical laboratory tests for all indications [24 months]
Secondary Outcome Measures
- Maximum observed concentration (Cmax) following intravenous administration for all indications [24 months]
- Minimum observed concentration (Cmin) following intravenous administration for all indications [24 months]
- Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications [24 months]
- Accumulation following multiple dosing for all indications [24 months]
- Half-life (t1/2) following intravenous administration for all indications [24 months]
- Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for all indications [24 months]
- Duration of Response (DOR) for all indications [24 months]
- Time to Response (TTR) [24 months]
- 9-month Progression-Free Survival (PFS) for all indications [9 months]
- 9-month Overall Survival (OS) for all indications [9 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject has provided informed consent prior to initiation of any study-specific activities/procedures
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Age greater than or equal to 18 years old at the time of signing the informed consent
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Histologically or cytologically confirmed Small Cell Lung Cancer (SCLC):
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Part A, C, D, E, F, and G: RR SCLC who progressed or recurred following platinum-based regimen;
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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Subjects with treated brain metastases are eligible provided they meet defined criteria
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Adequate organ function as defined in protocol
Exclusion Criteria:
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History of other malignancy within the past 2 years prior to first dose of AMG 757 with exceptions
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Major surgery within 28 days of first dose AMG 757
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Untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease
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Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of AMG 757
Exceptions:
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Subjects 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
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Prior palliative radiotherapy must have been completed at least 7 days before the first dose of AMG 757
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Subjects who experienced severe, life-threatening or recurrent (Grade 2 or higher) immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immune-oncology agents.
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Has evidence of interstitial lung disease or active, non-infectious pneumonitis
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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 AMG 757
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Part C only: history of solid organ transplantation or active autoimmune disease that has required systemic treatment within the past 2 years
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No evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If history of SARS-CoV-2, no acute symptoms of coronavirus disease 2019 (COVID-19) within14 days prior to first dose of investigational product (counted from day of positive test for asymptomatic subjects)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | City of Hope National Medical Center | Duarte | California | United States | 91010 |
2 | Yale New Haven Hospital | New Haven | Connecticut | United States | 06510 |
3 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
4 | Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
5 | University of Chicago | Chicago | Illinois | United States | 60637 |
6 | John Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | United States | 21287 |
7 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
8 | Washington University | Saint Louis | Missouri | United States | 63110-1093 |
9 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10021 |
10 | University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
11 | The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic | Columbus | Ohio | United States | 43210 |
12 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
13 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
14 | Chris OBrien Lifehouse | Camperdown | New South Wales | Australia | 2050 |
15 | Medizinische Universitaet Graz | Graz | Austria | 8036 | |
16 | Universitaetsklinikum Salzburg | Salzburg | Austria | 5020 | |
17 | Gustave Roussy | Villejuif | France | 94805 | |
18 | Universitätsklinikum Würzburg | Würzburg | Germany | 97078 | |
19 | National Cancer Center Hospital East | Kashiwa-shi | Chiba | Japan | 277-8577 |
20 | National Cancer Center Hospital | Chuo-ku | Tokyo | Japan | 104-0045 |
21 | Wakayama Medical University Hospital | Wakayama-shi | Wakayama | Japan | 641-8510 |
22 | Nederlands Kanker Instituut, Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | Netherlands | 1066 CX | |
23 | Maastricht Universitair Medisch Centrum | Maastricht | Netherlands | 6229 HX | |
24 | Biokinetica SA | Jozefow | Poland | 05-410 | |
25 | Europejskie Centrum Zdrowia Otwock Szpital imienia Fryderyka Chopina | Otwock | Poland | 05-400 | |
26 | Hospital Universitari Vall d Hebron | Barcelona | Cataluña | Spain | 08035 |
27 | Hospital Clinic i Provincial de Barcelona | Barcelona | Cataluña | Spain | 08036 |
28 | Hospital Universitario Ramon y Cajal | Madrid | Spain | 28034 | |
29 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
30 | Hospital Universitario La Paz | Madrid | Spain | 28046 | |
31 | Centre Hospitalier Universitaire Vaudois | Lausanne | Switzerland | 1011 | |
32 | Kantonsspital St Gallen | Sankt Gallen | Switzerland | 9007 | |
33 | Christie Hospital | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20160323