AMG 404 in Patients With Advanced Solid Tumors

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

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AMG 404

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris Obrien Lifehouse
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
• Belgium
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
• Brazil
  • Rio de Janeiro, Brazil, 22793-080
    • Instituto Coi
  • Bahia
    • Salvador, Bahia, Brazil, 40170-110
      • Nucleo de Oncologia da Bahia
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01308-050
      • Sociedade Beneficente de Senhoras Hospital Sirio Libanes
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Wakayama
    • Wakayama-shi, Wakayama, Japan, 641-8510
      • Wakayama Medical University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea Seoul St Marys Hospital
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Hospital Universitari Vall d Hebron
• Taiwan
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
• Turkey
  • Ankara, Turkey, 06200
    • Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
  • Istanbul, Turkey, 34010
    • Koc Universitesi Hastanesi
  • Izmir, Turkey, 35100
    • Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center LLC
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville James Graham Brown Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 2	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 3	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 4	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 6	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 7	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 8	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Experimental: Cohort 9	Drug: AMG 404; AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to Day 28
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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)
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.	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)
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.	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)
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.	Day 1 pre-dose and Day 15
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.	Up to approximately 54 months
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.	Up to approximately 43 months
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.	Up to approximately 54 months
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.	Up to approximately 54 months
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.	Up to approximately 48 months

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

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 (Actual): July 20, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• 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