- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03853109
AMG 404 in Patients With Advanced Solid Tumors
February 8, 2024 updated by: Amgen
A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 404, a Programmed Death-1 (PD-1) Antibody, in Patients With Advanced Solid Tumors
To evaluate the safety and tolerability of AMG 404, a monoclonal antibody that binds to PD-1 and inhibits its engagement with ligands, in patients with advanced solid tumors.
Study Overview
Study Type
Interventional
Enrollment (Actual)
171
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Chris OBrien Lifehouse
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South Australia
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Woodville South, South Australia, Australia, 5011
- The Queen Elizabeth Hospital
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Edegem, Belgium, 2650
- Universitair Ziekenhuis Antwerpen
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Rio de Janeiro, Brazil, 22793-080
- Instituto Coi
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Bahia
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Salvador, Bahia, Brazil, 40170-110
- Nucleo de Oncologia da Bahia
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Rio Grande Do Sul
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Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
- Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
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São Paulo
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Sao Paulo, São Paulo, Brazil, 01308-050
- Sociedade Beneficente de Senhoras Hospital Sírio Libanês
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São José do Rio Preto, São Paulo, Brazil, 15090-000
- Hospital de Base de Sao Jose do Rio Preto
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Alberta
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Calgary, Alberta, Canada, T2N 4N2
- Tom Baker Cancer Centre
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Chiba
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Kashiwa-shi, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
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Ehime
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Matsuyama-shi, Ehime, Japan, 791-0280
- National Hospital Organization Shikoku Cancer Center
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Wakayama
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Wakayama-shi, Wakayama, Japan, 641-8510
- Wakayama Medical University Hospital
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Seoul, Korea, Republic of, 03080
- Seoul National University Hospital
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Seoul, Korea, Republic of, 05505
- Asan Medical Center
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Seoul, Korea, Republic of, 03722
- Severance Hospital Yonsei University Health System
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Seoul, Korea, Republic of, 06351
- Samsung Medical Center
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Seoul, Korea, Republic of, 06591
- The Catholic University of Korea Seoul St Marys Hospital
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Gdansk, Poland, 80-214
- Uniwersyteckie Centrum Kliniczne
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Warszawa, Poland, 02-781
- Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
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Singapore, Singapore, 119074
- National University Hospital
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Singapore, Singapore, 169610
- National Cancer Centre Singapore
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Madrid, Spain, 28046
- Hospital Universitario La Paz
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Cataluña
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Barcelona, Cataluña, Spain, 08035
- Hospital Universitari Vall d Hebron
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Taipei, Taiwan, 11217
- Taipei Veterans General Hospital
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Taoyuan, Taiwan, 33305
- Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
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Ankara, Turkey, 06200
- Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
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Istanbul, Turkey, 34010
- Koc Universitesi Hastanesi
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Izmir, Turkey, 35100
- Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
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London, United Kingdom, W1G 6AD
- Sarah Cannon Research Institute UK
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California
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Santa Monica, California, United States, 90403
- Sarcoma Oncology Research Center LLC
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Colorado
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Denver, Colorado, United States, 80218
- Sarah Cannon Research Institute at HealthONE
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Kentucky
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Louisville, Kentucky, United States, 40202
- University of Louisville James Graham Brown Cancer Center
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
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Texas
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Houston, Texas, United States, 77030
- University of Texas MD Anderson Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 100 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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 informed consent.
- Life expectancy of greater than 3 months, in the opinion of the investigator
- Subject must have histologically or cytologically confirmed metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation.
- Cohort 7: participant must have one of the following tumor types: melanoma, small cell lung cancer, NSCLC (PD-L1 positive), head and neck squamous cell cancer (PD-L1 positive), urothelial (PD-L1 positive), gastric or GEJ adenocarcinoma (PD-L1 positive), esophageal (squamous, PD-L1 positive), cervical (PD-L1 positive), hepatocellular carcinoma, merkel cell carcinoma, squamous cell carcinoma of the skin, renal cell carcinoma (clear cell) subtypes of sarcoma (undifferentiated pleiomorphic / malignant fibrous histiocytoma, poorly differentiated and/or dedifferentiated liposarcoma, alveolar soft tissue sarcoma, angiosarcoma), thymic carcinoma, nasopharyngeal carcinoma (EBV positive), mesothelioma
- Cohort 8: participant must be MSI-H or MMR-deficient
- Cohort 9: participant must have NSCLC, PD-L1 positive, TPS ≥ 50%; not have EGFR or ALK or ROS1 genomic tumor aberrations and may not have received prior systemic treatment for the advanced disease (prior neoadjuvant, adjuvant, or concurrent chemoradiation is allowed).
- At least 1 measurable as defined by modified RECIST 1.1 which has not undergone biopsy within 3 months of the screening scan. This lesion cannot be biopsied at any time during the study. Note: if there is only one lesion available for biopsy and radiographic assessment, it may be permitted to be biopsied after discussion with sponsor.
- Subjects with treated brain metastases are eligible provided they meet the following criteria: Definitive therapy was completed at least 2 weeks prior to enrollment. No evidence of radiographic CNS progression or CNS disease following definitive therapy and by the time of study screening. Patients manifesting progression in lesions previously treated with stereotactic radiosurgery may still be eligible if pseudoprogression can be demonstrated by appropriate means and after discussion with the medical monitor.
- Any CNS disease is asymptomatic, any neurologic symptoms due to CNS disease have returned to baseline or are deemed irreversible, the patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off or on stable doses of anti-epileptic drugs for malignant CNS disease.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2.
- Hematologic function, as follows without growth factor support within 2 weeks prior to study day 1: Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10E9/L; Platelet count greater than or equal to 75 x 10E9/L; Hemoglobin greater than or equal to 9 g/dL (90 g/L).
- Adequate renal laboratory assessments, as follows: Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation . 60 ml/min/1.73 m^2 for Cohorts 1, 2, and 4 Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation >= 45 ml/min/1.73 m^2 for Cohorts 3, 6, 7, 8 and 9.
- Hepatic function, as follows: Total bilirubin less than or equal to 1.5 x ULN or less than or equal to 3 x ULN for subjects with liver metastasis; AST less than or equal to 3 x ULN or less than or equal to' 5 x ULN for subjects with liver metastasis; ALT less than or equal to 3 x ULN or less than or equal to 5 x ULN for subjects with liver metastasis; Alkaline phosphatase less than or equal to 2.5 x ULN or less than or equal to 5 x ULN for subjects with liver metastasis (Note: elevated alkaline phosphatase is acceptable if it is due to non-hepatic associated pathology [eg, bone disease]).
- Subjects enrolled to Cohorts 7-9 must submit tumor tissue sample. Fresh tumor biopsies may be performed if subject has a readily accessible tumor lesion and who consent to the biopsies. If fresh biopsies cannot be obtained, archival tumor samples are acceptable. Prior to enrollment it is required to determine that there is enough tumor tissue available to be sent to the central laboratory: Cohorts 7 and 9: Archival tissue collected up to 12 months prior to screening date is permitted. Biopsies collected between 12-18 months prior to screening are allowed upon discussion with the medical monitor. Subjects with EBV associated nasopharyngeal carcinoma may submit biopsy with EBV test results from within 36 months prior to screening; Cohort 8: Archival tissue with MSI-high/dMMR test results collected up to 36 months prior to screening is permitted.
Exclusion Criteria:
- Disease Related. Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal disease (exception: benign asymptomatic tumors are permitted).
- Other Medical Conditions. History of other malignancy within the past 2 years, with the following exception[s]: Malignancy treated with curative intent and with no known active disease present for greater than or equal to 2 years before enrollment and felt to be at low risk for recurrence by the treating physician. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated cervical carcinoma in situ without evidence of disease. Adequately treated breast ductal carcinoma in situ without evidence of disease. Prostatic intraepithelial neoplasia without evidence of prostate cancer. Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. Other malignancies which do not require systemic therapy, may be considered upon discussion with the medical monitor.
- History of solid organ transplantation.
- Major surgery within 28 days of study day 1.
- Prior/Concomitant Therapy: Prior treatment with anti-programmed death 1 (PD-1), anti-PD-L1, CTLA-4 or other checkpoint inhibitor drugs
- Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 21 days prior to study day 1. Note: Palliative radiotherapy is permitted.
- Live vaccine therapy within 4 weeks prior to study drug administration.
- Current treatment or within 14 days of day 1 with immunosuppressive corticosteroid defined as greater than 10 mg prednisone daily or equivalent. Corticosteroids with no or minimal systemic effect (such as topical or inhalation) are permitted. Note: Corticosteroids > 10 mg prednisone used for management of contrast allergy for study scans is allowed.
- Prior/Concurrent Clinical Study Experience: Currently receiving treatment in another investigational device or drug study, or less than 21 days prior to study day 1 since ending treatment on another investigational device or drug study(ies).
- Diagnostic Assessments: Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis.
- History of allergic reactions or acute hypersensitivity reaction to antibody therapies.
- Positive/Non-negative test for Human Immunodeficiency Virus (HIV).
- Has known active Hepatitis B (eg, hepatitis B antigen [HBsAg] reactive) or Hepatitis C (eg, HCV RNA [qualitative] is detected).
- Subject currently has an active infection requiring systemic therapy.
- Active or history of any autoimmune disease or immunodeficiencies. Subjects with Type I diabetes, vitiligo, psoriasis, hypo- or hyper- thyroid disease not requiring immunosuppressive treatment are permitted.
- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association greater than class II), unstable angina, or cardiac arrhythmia requiring antiarrhythmic medication.
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or are stable and well controlled with minimal, local, or non-invasive intervention AND there is agreement to allow by both the investigator and the Amgen Medical Monitor.
- Other Exclusions: Males and females of reproductive potential who are unwilling to practice highly effective methods of birth control while on study through 6 months (females) and 8 months (males) after receiving the last dose of AMG 404.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort 1
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 2
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 3
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 4
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 6
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 7
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 8
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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Experimental: Cohort 9
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AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Subject incidence of Dose limiting toxicities (DLTs)
Time Frame: 28 Days
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Dose limiting toxicities (DLTs)
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28 Days
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Subject incidence of treatment emergent adverse events
Time Frame: 28 Days
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28 Days
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Subject incidence of treatment related adverse events
Time Frame: 28 Days
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28 Days
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Subject incidence of changes in vital signs
Time Frame: 28 Days
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28 Days
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Subject incidence of clinical laboratory tests
Time Frame: 28 Days
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28 Days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Maximum observed concentration (Cmax) of AMG 404
Time Frame: 24 months
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Pharmacokinetic (PK) analysis of AMG 404
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24 months
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Time of maximum observed concentration (Tmax) of AMG 404
Time Frame: 24 months
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Pharmacokinetic (PK) analysis of AMG 404
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24 months
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Area under the serum concentration-time curve (AUC) of AMG 404
Time Frame: 24 months
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Pharmacokinetic (PK) analysis of AMG 404
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24 months
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Subject incidence of anti-AMG 404 antibodies
Time Frame: 24 months
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Assess immunogenicity
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24 months
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Objective tumor response
Time Frame: 24 months
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24 months
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Duration of overall response
Time Frame: 24 months
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24 months
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Progression-free survival
Time Frame: 24 months
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24 months
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Disease control rate (DCR)
Time Frame: 24 months
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24 months
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Duration of stable disease
Time Frame: 48 months
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48 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: MD, Amgen
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 5, 2019
Primary Completion (Actual)
July 19, 2022
Study Completion (Actual)
November 2, 2023
Study Registration Dates
First Submitted
February 22, 2019
First Submitted That Met QC Criteria
February 22, 2019
First Posted (Actual)
February 25, 2019
Study Record Updates
Last Update Posted (Estimated)
February 9, 2024
Last Update Submitted That Met QC Criteria
February 8, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20180143
- 2018-004268-80 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
IPD Sharing 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 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.
IPD Sharing 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.
If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision.
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 URL below.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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