AMG 404 in Patients With Advanced Solid Tumors

NCT03853109 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 201801432018-004268-80
• Study Type: interventional
• Target: 171
• Locations: 13 countries
• Sites: 34

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

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

  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

  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

  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

  Day 1 pre-dose and Day 15

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

  Up to approximately 54 months

Study Arms (8)

Cohort 1

EXPERIMENTAL

Cohort 1

Drug: AMG 404

Cohort 2

EXPERIMENTAL

Cohort 2

Drug: AMG 404

Cohort 3

EXPERIMENTAL

Cohort 3

Drug: AMG 404

Cohort 4

EXPERIMENTAL

Cohort 4

Drug: AMG 404

Cohort 6

EXPERIMENTAL

Cohort 6

Drug: AMG 404

Cohort 7

EXPERIMENTAL

Cohort 7

Drug: AMG 404

Cohort 8

EXPERIMENTAL

Cohort 8

Drug: AMG 404

Cohort 9

EXPERIMENTAL

Cohort 9

Drug: AMG 404

Interventions

AMG 404 DRUG

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 6; Cohort 7; Cohort 8; Cohort 9

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (34)

Sarcoma Oncology Research Center LLC

Santa Monica, California, 90403, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Nucleo de Oncologia da Bahia

Salvador, Estado de Bahia, 40170-110, Brazil

Location

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

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

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

Location

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

São Paulo, São Paulo, 01308-050, Brazil

Location

Instituto Coi

Rio de Janeiro, 22793-080, Brazil

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

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

Warsaw, 02-781, Poland

Location

National University Hospital

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, 06200, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi

Istanbul, 34010, Turkey (Türkiye)

Location

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

Izmir, 35100, Turkey (Türkiye)

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40316348 BACKGROUND

Related Links

• AmgenTrials clinical trials website

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: February 25, 2019
• Study Start: March 5, 2019
• Primary Completion: July 19, 2022
• Study Completion: November 2, 2023
• Last Updated: July 20, 2025
• Results First Posted: December 13, 2024

Record last verified: 2025-07

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 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. 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.

Locations

JP (3); CA (1); BR (5); BE (1); US (5); TW (2); GB (1); AU (2); SG (2); PL (2); ES (2); TU (3); KR (5)