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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02713529
Recruitment Status : Completed
First Posted : March 18, 2016
Results First Posted : June 1, 2020
Last Update Posted : July 17, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Amgen

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 117 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Participants With Dose Limiting Toxicities (DLT) [ Time Frame: The DLT evaluation period was Day 1 to Day 21 ]
    DLTs were evaluated by the Dose Level Review Team (DLRT). A DLT was defined as any grade >=3 adverse event occurring during a DLT time window (21 day period from the initial administration of AMG 820 and pembrolizumab in combination), and if judged by the investigator to be related to the administration of AMG 820 and/or pembrolizumab.

  2. Participants With Treatment -Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2 ]
    TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.

  3. Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment [ Time Frame: Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2 ]
    TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.

  4. Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment [ Time Frame: Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2 ]
    TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.

  5. Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) [ Time Frame: Baseline: Day -28; Treatment: up to Month 13.7 ]

    ORR was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). During treatment radiographic imaging was performed at Week 10 and repeated at least every 10 weeks until disease progression.

    Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required.



Secondary Outcome Measures :
  1. Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded [ Time Frame: Day 1 up to Month 16 (max time to censoring) ]
    Time to response was defined as the time from first dose of AMG 820 until first documented complete or partial response per irRECIST divided by 365.25 days/12.

  2. Time to Progression (TTP) for Participants Who Had Progressive Disease [ Time Frame: Day 1 up to 14.4 months (max time to censoring) ]
    Time to progression was defined as the time from first dose of AMG 820 until first documented progressive disease per irRECIST divided by 365.25 days/12.

  3. Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 [ Time Frame: Day 1 up to Month 6 or Month 12 ]
    Overall survival time was calculated as the number of days from the first administration of AMG 820 to date of death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive at Month 6 and Month 12.

  4. Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12 [ Time Frame: Day 1 up to Month 6 or Month 12 ]
    Progression-free survival time was calculated as the number of days from the first administration of AMG 820 to date of progressive disease or death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive and progression-free at Month 6 and Month 12.

  5. AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
  6. AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
  7. AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
    AUClast is the area under the serum concentration-time curve from time zero to time of last quantifiable concentration.

  8. AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
    AUCtau is the area under the serum concentration-time curve over the dose interval tau, with tau equal to 21 days.

  9. AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
  10. AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
  11. AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
    Volume of distribution observed at terminal phase after intravenous dosing.

  12. AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
    Drug clearance observed after intravenous dosing.

  13. AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR) [ Time Frame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36 ]
    Accumulation ratio is AUCtau following administration in Cycle 2 / AUCtau after administration in Cycle 1



Information from the National Library of Medicine

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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 within 3 months prior to enrollment, when feasible.

Exclusion Criteria:

  • Has known active central nervous system metastases and/or carcinomatous meningitis.
  • 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 Common Terminology Criteria for Adverse Events (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02713529


Locations
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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
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] June 15, 2018
Statistical Analysis Plan  [PDF] February 6, 2019

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02713529    
Other Study ID Numbers: 20150195
MASTERKEY ( Other Identifier: Amgen )
2016-001080-36 ( EudraCT Number )
KEYNOTE-347 ( Other Identifier: Merck )
First Posted: March 18, 2016    Key Record Dates
Results First Posted: June 1, 2020
Last Update Posted: July 17, 2020
Last Verified: July 2020
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

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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:
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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