AMG 404 in Patients With Advanced Solid Tumors

Sponsor

Amgen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03853109

Collaborator

(none)

170

Enrollment

Locations

Arms

88.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: AMG 404	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

170 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 5, 2019

Actual Primary Completion Date :

Jul 19, 2022

Anticipated Study Completion Date :

Jul 19, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 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 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 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 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 5 Cohort 5	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 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 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 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 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.

Outcome Measures

Primary Outcome Measures

Subject incidence of Dose limiting toxicities (DLTs) [28 Days]
Dose limiting toxicities (DLTs)
Subject incidence of treatment emergent adverse events [28 Days]
Subject incidence of treatment related adverse events [28 Days]
Subject incidence of changes in vital signs [28 Days]
Subject incidence of clinical laboratory tests [28 Days]

Secondary Outcome Measures

Maximum observed concentration (Cmax) of AMG 404 [24 months]
Pharmacokinetic (PK) analysis of AMG 404
Time of maximum observed concentration (Tmax) of AMG 404 [24 months]
Pharmacokinetic (PK) analysis of AMG 404
Area under the serum concentration-time curve (AUC) of AMG 404 [24 months]
Pharmacokinetic (PK) analysis of AMG 404
Subject incidence of anti-AMG 404 antibodies [24 months]
Assess immunogenicity
Objective tumor response [24 months]
Duration of overall response [24 months]
Progression-free survival [24 months]
Disease control rate (DCR) [24 months]
Duration of stable disease [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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

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, 4 and 5.

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]).
Cohort 5 only: Subject is a resident in China, Taiwan, or Hong Kong.
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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

Amgen

Investigators

Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

AmgenTrials clinical trials website

Publications

None provided.

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT03853109

Other Study ID Numbers:

20180143
2018-004268-80

First Posted:

Feb 25, 2019

Last Update Posted:

Aug 19, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Aug 19, 2022