AzTrials
AzTrials

Advanced Solid TumorsPhase 1NCT03853109

AMG 404 in Patients With Advanced Solid Tumors

A Phase 1 study testing AMG 404 in people with Advanced Solid Tumors, run by Amgen at 34 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Advanced Solid Tumors
What is being tested?
AMG 404
Could I receive a placebo?
No, everyone receives an active treatment
How many people
171 participants
Where
34 sitesin 13 countries
Study dates
5 Mar 2019to 2 Nov 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.

Trial locations and contacts

34 sites in 13 countries.

34 sites in 13 countries

United States5 sites

  • Sarah Cannon Research Institute at HealthONE

    Denver, Colorado, 80218

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Louisville James Graham Brown Cancer Center

    Louisville, Kentucky, 40202

  • Sarcoma Oncology Research Center LLC

    Santa Monica, California, 90403

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Brazil5 sites

  • Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Instituto Coi

    Rio de Janeiro, 22793-080

  • Nucleo de Oncologia da Bahia

    Salvador, Estado de Bahia, 40170-110

  • Hospital de Base de Sao Jose do Rio Preto

    São José do Rio Preto, São Paulo, 15090-000

  • Sociedade Beneficente de Senhoras Hospital Sirio Libanes

    São Paulo, São Paulo, 01308-050

Other trials in Brazil

South Korea5 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • The Catholic University of Korea Seoul St Marys Hospital

    Seoul, 06591

Other trials in South Korea

Japan3 sites

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

  • National Hospital Organization Shikoku Cancer Center

    Matsuyama, Ehime, 791-0280

  • Wakayama Medical University Hospital

    Wakayama, Wakayama, 641-8510

Other trials in Japan

Turkey (Türkiye)3 sites

  • Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

    Ankara, 06200

  • Koc Universitesi Hastanesi

    Istanbul, 34010

  • Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)

    Izmir, 35100

Other trials in Turkey (Türkiye)

Australia2 sites

  • Chris OBrien Lifehouse

    Camperdown, New South Wales, 2050

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

Poland2 sites

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-214

  • Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

    Warsaw, 02-781

Other trials in Poland

Singapore2 sites

  • National University Hospital

    Singapore, 119074

  • National Cancer Centre Singapore

    Singapore, 169610

Other trials in Singapore

Spain2 sites

  • Hospital Universitari Vall d Hebron

    Barcelona, Catalonia, 08035

  • Hospital Universitario La Paz

    Madrid, 28046

Other trials in Spain

Taiwan2 sites

  • Taipei Veterans General Hospital

    Taipei, 11217

  • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

    Taoyuan, 33305

Other trials in Taiwan

Belgium1 site

  • Universitair Ziekenhuis Antwerpen

    Edegem, 2650

Other trials in Belgium

Canada1 site

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

Other trials in Canada

United Kingdom1 site

  • Sarah Cannon Research Institute UK

    London, W1G 6AD

Other trials in United Kingdom

About this study

Official title: 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.

Being tested
AMG 404

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AMG 404Drug

    AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.

Study groups in NCT03853109
Study groupRoleWhat they receive
Cohort 1ExperimentalCohort 1
Receives: Drug: AMG 404
Cohort 2ExperimentalCohort 2
Receives: Drug: AMG 404
Cohort 3ExperimentalCohort 3
Receives: Drug: AMG 404
Cohort 4ExperimentalCohort 4
Receives: Drug: AMG 404
Cohort 6ExperimentalCohort 6
Receives: Drug: AMG 404
Cohort 7ExperimentalCohort 7
Receives: Drug: AMG 404
Cohort 8ExperimentalCohort 8
Receives: Drug: AMG 404
Cohort 9ExperimentalCohort 9
Receives: Drug: AMG 404

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

    Toxicities were graded with the Common Terminology Criteria for Adverse Events CTCAE v5.0., the following toxicities were classified as DLTs:

    • Any treatment related grade 5 toxicity
    • Grade 4 neutropenia or thrombocytopenia
    • Febrile neutropenia
    • Grade 4 anemia
    • Grade 3 or 4 non-hematologic toxicity
    • Recurrent grade 2 pneumonitis
    • Any other toxicity requiring permanent discontinuation of AMG 404.

    Measured: Up to Day 28

  2. Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

    A TEAE is any adverse event (AE) starting on or after the first administration of investigational product (IP) and up to and including 140 days after the last IP dose date or end of the study, whichever occurs earlier. A TEAE with unknown/missing relatedness to AMG 404 is assumed as an event is related to AMG 404. A serious adverse event (SAE) is defined as an adverse event that: is fatal, is life threatening, requires in-patient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important serious event. A treatment-related AE (TRAE) is any TEAE that per investigator review has a reasonable possibility of being caused by the investigational product. In the unlikely event that the relationship is missing, the TEAE will be considered TRAE and documented in a footnote of the treatment-related summary.

    Measured: Up to the last dose of AMG 404 + 140 days (approximately 46 months); median (min, max) exposure to AMG 404 was 3.58 (0.02, 41.7) months

Secondary outcomes (9)

  1. AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2

    Maximum concentration of AMG 404 in blood serum at different time points.

    Measured: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)

  2. AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2

    Tmax represents the time to reach Cmax in the blood serum.

    Measured: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)

  3. AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2

    Assessment of AMG 404 exposure over 28 days.

    Measured: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)

  4. Number of Participants With Anti-AMG 404 Antibodies

    Transient was defined as the number of participants with negative result at the participant's last time point tested within the study period. Only participants with both baseline and post-baseline are included.

    Measured: Day 1 pre-dose and Day 15

  5. Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1

    Objective response was defined as a tumor response assessment of either complete response (CR) (disappearance of all target lesions) or partial response (PR) (at least a 30% decrease in the sum of the diameters of target lesions) measured by positron emission tomography(PET)/computed tomography (CT), CT or magnetic resonance imaging (MRI) and assessed per RECIST v1.1. Participants who did not experience PR/CR or did not have any follow-up tumor assessments was regarded as non-responders. This endpoint was determined only for participants with measurable disease at baseline.

    Measured: Up to approximately 54 months

  6. Duration of Response (DOR) Per Modified RECIST v1.1

    DOR was defined as the time from the first documentation of objective response (CR or PR) until the first documentation of disease progression or death due to any cause, whichever occurred first. Only participants who achieved objective response were evaluated for DOR. DOR was censored at the last evaluable post-baseline tumor assessment date; otherwise, at the first dose of IP.

    Kaplan-Meier (KM) analysis was used to estimate DOR for responders, providing a median value and 80% confidence intervals (CI) where sufficient data were available. The Brookmeyer and Crowley method was used to calculate confidence intervals. For cohorts with limited responders or heavily censored data, the median DOR or CI bounds could not be calculated.

    Measured: Up to approximately 43 months

  7. Disease Control Rate (DCR) Per Modified RECIST v1.1

    DCR was defined as the percentage of participants in whom objective response (CR or PR) or stable disease (SD) was determined as per RECIST v1.1.

    Measured: Up to approximately 54 months

  8. Duration of Stable Disease (DoSD) Per Modified RECIST v1.1

    DoSD was measured from the start of treatment until the first documentation of disease progression or death due to any cause. DoSD was calculated only in participants with the best overall response of SD, defined as neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for PD.

    KM analysis was used to estimate the median DoSD, and CIs were calculated using the Brookmeyer and Crowley method. DoSD was censored at the last evaluable post-baseline tumor assessment date or at the first dose of IP, if no progression or death was documented.

    Measured: Up to approximately 54 months

  9. Progression-free Survival (PFS) Per Modified RECIST v1.1

    PFS was defined as the time from the first dose of IP unite the first documentation of radiological disease progression or death due to any cause, whichever occurred first in the absence of subsequent anticancer therapy.

    Measured: Up to approximately 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2019
  2. Study start5 Mar 2019
  3. Primary completion19 Jul 2022
  4. Study completion2 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
171 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03853109
Sponsor's protocol ID
20180143
Other IDs
2018-004268-80, 2018
Status last verified
Jul 2025
First submitted
22 Feb 2019
Last updated
20 Jul 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Publications

  • Price T, Lugowska I, Chawla SP, Falchook G, Subbiah V, Monzon JG, Arkenau HT, Hui M, Kuboki Y, Dziadziuszko R, Shibaki R, Hong MH, Tan D, Rocha Lima CM, Wang K, Hindoyan A, Shi W, Wong H, Kistler M, Prenen H. A phase I, open-label, multicentre, first-in-human study to evaluate safety, pharmacokinetics and efficacy of AMG 404, a PD-1 inhibitor, in patients with advanced solid tumours. BMJ Open. 2025 May 2;15(5):e088578. doi: 10.1136/bmjopen-2024-088578.

    PubMed 40316348

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AMG 404 in people with Advanced Solid Tumors, run by Amgen at 34 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Brazil, South Korea, Japan, Turkey (Türkiye) and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) (time frame: Up to Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03853109, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in