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

NCT02713529 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 20150195MASTERKEY2016-001080-36KEYNOTE-347
• Study Type: interventional
• Target: 117
• Locations: 6 countries
• Sites: 15

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Participants With Dose Limiting Toxicities (DLT)

  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.

  The DLT evaluation period was Day 1 to Day 21

• Participants With Treatment -Emergent Adverse Events (TEAEs)

  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.

  Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2

• Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment

  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.

  Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2

• Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment

  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.

  Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2

• Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST)

  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.

  Baseline: Day -28; Treatment: up to Month 13.7

Secondary Outcomes (13)

• Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded

  Day 1 up to Month 16 (max time to censoring)

• Time to Progression (TTP) for Participants Who Had Progressive Disease

  Day 1 up to 14.4 months (max time to censoring)

• Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12

  Day 1 up to Month 6 or Month 12

• Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12

  Day 1 up to Month 6 or Month 12

• AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2

  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

Study Arms (1)

AMG820 and pembrolizumab

EXPERIMENTAL

Treatment with AMG820 and pembrolizumab

Biological: AMG820 and pembrolizumab

Interventions

AMG820 and pembrolizumab BIOLOGICAL

Treatment with AMG820 and pembrolizumab

AMG820 and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AmMax Bio, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (15)

Research Site

Atlanta, Georgia, 30332, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Grand Rapids, Michigan, 49546, United States

Location

Research Site

New York, New York, 10021, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Research Site

Greenville, South Carolina, 29605, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Research Site

Camperdown, New South Wales, 2050, Australia

Location

Research Site

Parkville, Victoria, 3050, Australia

Location

Research Site

Wilrijk, 2610, Belgium

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Related Publications (1)

• Razak AR, Cleary JM, Moreno V, Boyer M, Calvo Aller E, Edenfield W, Tie J, Harvey RD, Rutten A, Shah MA, Olszanski AJ, Jager D, Lakhani N, Ryan DP, Rasmussen E, Juan G, Wong H, Soman N, Smit MD, Nagorsen D, Papadopoulos KP. Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors. J Immunother Cancer. 2020 Oct;8(2):e001006. doi: 10.1136/jitc-2020-001006.

  PMID: 33046621 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2016
• First Posted: March 18, 2016
• Study Start: April 14, 2016
• Primary Completion: January 2, 2019
• Study Completion: May 17, 2019
• Last Updated: January 20, 2023
• Results First Posted: June 1, 2020

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

BE (1); US (8); AU (2); CA (1); DE (1); ES (2)