Clincosm LogoSign in Get a demo

Study Evaluating Safety, Tolerability and PK of AMG 757 in Adults With Small Cell Lung Cancer

Sponsor
Amgen (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03319940
Collaborator
(none)
382
Enrollment
33
Locations
6
Arms
85.8
Anticipated Duration (Months)
11.6
Patients Per Site
0.1
Patients Per Site Per Month

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

Study Type:
Interventional
Anticipated Enrollment :
382 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model 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 in subjects with Small Cell Lung Cancer. The dose exploration phases of the study will estimate the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of AMG 757 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.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 in subjects with Small Cell Lung Cancer. The dose exploration phases of the study will estimate the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of AMG 757 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.
Masking:
None (Open Label)
Masking Description:
The patient, investigator, investigative staff, medical monitor and care provider will not be masked for the study.
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of AMG 757 in Subjects With Small Cell Lung Cancer
Actual Study Start Date :
Dec 26, 2017
Anticipated Primary Completion Date :
Feb 20, 2025
Anticipated Study Completion Date :
Feb 20, 2025

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

  1. Number of participants with dose limiting toxicities (DLT) for all indications [6 months]

  2. Number of participants with treatment-emergent adverse events (AEs) for all indications [24 months]

  3. Number of participants with treatment-related AEs for all indications [24 months]

  4. Number of participants with clinically significant changes in vital signs for all indications [24 months]

  5. Number of participants with significant changes in ECG for all indications [24 months]

  6. Number of participants with significant changes in physical examinations for all indications [24 months]

  7. Number of participants with significant changes in clinical laboratory tests for all indications [24 months]

Secondary Outcome Measures

  1. Maximum observed concentration (Cmax) following intravenous administration for all indications [24 months]

  2. Minimum observed concentration (Cmin) following intravenous administration for all indications [24 months]

  3. Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications [24 months]

  4. Accumulation following multiple dosing for all indications [24 months]

  5. Half-life (t1/2) following intravenous administration for all indications [24 months]

  6. Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for all indications [24 months]

  7. Duration of Response (DOR) for all indications [24 months]

  8. Time to Response (TTR) [24 months]

  9. 9-month Progression-Free Survival (PFS) for all indications [9 months]

  10. 9-month Overall Survival (OS) for all indications [9 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Subject 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 Small Cell Lung Cancer (SCLC):

  • Part A, C, D, E, F, and G: RR SCLC who progressed or recurred following platinum-based regimen;

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

  • Subjects 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 AMG 757 with exceptions

  • Major surgery within 28 days of first dose AMG 757

  • Untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease

  • Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of AMG 757

Exceptions:

  • 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

  • Prior palliative radiotherapy must have been completed at least 7 days before the first dose of AMG 757

  • 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.

  • 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 AMG 757

  • Part C only: history of solid organ transplantation or active autoimmune disease that has required systemic treatment within the past 2 years

  • 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.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT03319940
Other Study ID Numbers:
  • 20160323
First Posted:
Oct 24, 2017
Last Update Posted:
Jun 30, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Amgen
Half Life Extended (HLE) Bispecific T cell engager (BiTE®)
Delta-like protein 3 (DLL3)
Additional relevant MeSH terms:
Small Cell Lung Carcinoma
Pembrolizumab

Study Results

No Results Posted as of Jun 30, 2022