Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer

• ClinicalTrials.gov Identifier: NCT02713529
• Recruitment Status: Completed
• First Posted: March 18, 2016
• Last Update Posted: October 23, 2019
• Sponsor: Amgen
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

A multi-center Phase 1b/2 study testing the combination of AMG 820 and pembrolizumab in subjects with select advanced solid tumors.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer; Colorectal Cancer; Non-Small Cell Lung Cancer	Biological: AMG820 and pembrolizumab	Phase 1; Phase 2

Detailed Description:

Phase 1b is AMG 820 dose determining and aimed at assessing the safety and tolerability of the selected starting dose of AMG 820 in combination with pembrolizumab. Phase 2 of the study will further evaluate safety and tolerability and additionally test whether AMG 820 can enhance the anti-tumor activity observed historically with pembrolizumab alone and/or overcome lack of response to pembrolizumab monotherapy in subjects with select solid tumors.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase1b/2 Study Assessing Safety and Anti-tumor Activity of AMG 820 in Combination With Pembrolizumab in Select Advanced Solid Tumors
• Actual Study Start Date: April 14, 2016
• Actual Primary Completion Date: January 2, 2019
• Actual Study Completion Date: May 17, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: AMG820 and pembrolizumab; Treatment with AMG820 and pembrolizumab	Biological: AMG820 and pembrolizumab; Treatment with AMG820 and pembrolizumab

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment related adverse events as assessed by CTCAE version 4.0 [ Time Frame: 12 months ]
2. Objective response rate of tumors using irRECIST criteria for total measureable tumor burden [ Time Frame: 12 months ]
   Analyze CT/MRI scans using a modified criteria (irRECIST) adapting the immune-related response criteria to conventional RECIST 1.1 (irRECIST accounts for index and measureable lesions in total tumor burden).
3. Number of participants with treatment emergent adverse events as assessed by CTCAE version 4.0 [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. Objective response rate of tumors using RECIST 1.1 criteria for total measurable tumor burden [ Time Frame: 12 months ]
   Analyze CT/MRI scans using defined criteria for bidimensional measurements of index lesions.
2. Maximum observed concentration [Cmax] of AMG820 [ Time Frame: 12 months ]
   Analyze serum concentration of AMG 820 after intravenous infusion administration of AMG 820 in combination with pembrolizumab.
3. CD4, CD8, and CD68 cell numbers in pre-treatment tumor biopsy tissue [ Time Frame: 12 months ]
4. Minimum observed concentration [Cmin] of AMG 820 [ Time Frame: 12 months ]
   Analyze serum concentration of AMG 820 after intravenous infusion administration of AMG 820 in combination with pembrolizumab.
5. Area Under the Curve [AUC] of AMG820 [ Time Frame: 12 months ]
   Analyze serum concentration of AMG 820 after intravenous infusion administration of AMG 820 in combination with pembrolizumab.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Pathologically documented, advanced colorectal, pancreatic or non-small cell lung cancer that is refractory to standard treatment, or the subjects have been intolerant to or refuse standard treatment.
• Measurable disease per RECIST 1.1 guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Adequate hematologic, renal, and hepatic function determined by laboratory blood and urine tests.
• Availability of recent tumor tissue with 3 months prior to enrollment, when feasible.

Exclusion Criteria:

• Has known active central nervous system metastases
• History of other malignancy with the past 2 years with some exceptions
• Evidence of active non-infectious pneumonitis/interstitial lung disease
• Evidence of other active autoimmune disease that has required prolonged systemic treatment in past 2 years.
• Evidence of clinically significant immunosuppression such as organ or stem cell transplantation, any severe congenital or acquired cellular and/or humoral immune deficiency, concurrent opportunistic infection.
• Receiving systemic immunostimulatory agents within 6 weeks or 5 half-lives, whichever is shorter, prior to first dose of study treatment (except ant PD-1/PD-L1 treatment if recruited into Group 4a or 4b).
• Evidence of active infection within 2 weeks prior to first dose of study treatment.
• Prior chemotherapy, radiotherapy, biological cancer therapy or major surgery within 28 days prior to enrollment
• Currently participating or has participated in a study (treatment period only) of an investigational agent or used an investigational device within 28 days of enrollment
• Received live vaccine within 28 days prior to enrollment
• Adverse event due to cancer therapy administered more than 28 days prior to enrollment that has not recovered to CTCAE grade 1 or better.
• Positive for human immunodeficiency virus (HIV), Hepatitis B or C
• Women planning to become pregnant or who are lactating/breastfeeding while on study through 4 months after receiving the last dose of study drug.

Contacts and Locations

Locations

United States, Georgia

Research Site

Atlanta, Georgia, United States, 30332

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02114

Research Site

Boston, Massachusetts, United States, 02215

United States, Michigan

Research Site

Grand Rapids, Michigan, United States, 49546

United States, New York

Research Site

New York, New York, United States, 10021

United States, Pennsylvania

Research Site

Philadelphia, Pennsylvania, United States, 19111

United States, South Carolina

Research Site

Greenville, South Carolina, United States, 29605

United States, Texas

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States, 78229

Australia, New South Wales

Research Site

Camperdown, New South Wales, Australia, 2050

Australia, Victoria

Research Site

Parkville, Victoria, Australia, 3050

Belgium

Research Site

Wilrijk, Belgium, 2610

Canada, Ontario

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Germany

Research Site

Heidelberg, Germany, 69120

Spain

Research Site

Madrid, Spain, 28040

Research Site

Madrid, Spain, 28050

Sponsors and Collaborators

Amgen

Merck Sharp & Dohme Corp.

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02713529 History of Changes
• Other Study ID Numbers: 20150195; MASTERKEY ( Other Identifier: Amgen )
• First Posted: March 18, 2016
• Last Update Posted: October 23, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• URL: https://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:

Solid Tumor; Pancreatic Cancer; Colorectal Cancer; Non-Small Cell Lung Cancer

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents