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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03853109




Registration number
NCT03853109
Ethics application status
Date submitted
22/02/2019
Date registered
25/02/2019
Date last updated
9/02/2024

Titles & IDs
Public title
AMG 404 in Patients With Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
2018-004268-80
Secondary ID [2] 0 0
20180143
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 404

Experimental: Cohort 1 - Cohort 1

Experimental: Cohort 2 - Cohort 2

Experimental: Cohort 3 - Cohort 3

Experimental: Cohort 4 - Cohort 4

Experimental: Cohort 6 - Cohort 6

Experimental: Cohort 7 - Cohort 7

Experimental: Cohort 8 - Cohort 8

Experimental: Cohort 9 - Cohort 9


Treatment: Drugs: AMG 404
AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Subject incidence of Dose limiting toxicities (DLTs)
Timepoint [1] 0 0
28 Days
Primary outcome [2] 0 0
Subject incidence of treatment emergent adverse events
Timepoint [2] 0 0
28 Days
Primary outcome [3] 0 0
Subject incidence of treatment related adverse events
Timepoint [3] 0 0
28 Days
Primary outcome [4] 0 0
Subject incidence of changes in vital signs
Timepoint [4] 0 0
28 Days
Primary outcome [5] 0 0
Subject incidence of clinical laboratory tests
Timepoint [5] 0 0
28 Days
Secondary outcome [1] 0 0
Maximum observed concentration (Cmax) of AMG 404
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Time of maximum observed concentration (Tmax) of AMG 404
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Area under the serum concentration-time curve (AUC) of AMG 404
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Subject incidence of anti-AMG 404 antibodies
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Objective tumor response
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Duration of overall response
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Progression-free survival
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Disease control rate (DCR)
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Duration of stable disease
Timepoint [9] 0 0
48 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/11/2023
Sample size
Target
Accrual to date
Final
171
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Edegem
Country [7] 0 0
Brazil
State/province [7] 0 0
Bahia
Country [8] 0 0
Brazil
State/province [8] 0 0
Rio Grande Do Sul
Country [9] 0 0
Brazil
State/province [9] 0 0
São Paulo
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio de Janeiro
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Japan
State/province [12] 0 0
Chiba
Country [13] 0 0
Japan
State/province [13] 0 0
Ehime
Country [14] 0 0
Japan
State/province [14] 0 0
Wakayama
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Poland
State/province [16] 0 0
Gdansk
Country [17] 0 0
Poland
State/province [17] 0 0
Warszawa
Country [18] 0 0
Singapore
State/province [18] 0 0
Singapore
Country [19] 0 0
Spain
State/province [19] 0 0
Cataluña
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taipei
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taoyuan
Country [23] 0 0
Turkey
State/province [23] 0 0
Ankara
Country [24] 0 0
Turkey
State/province [24] 0 0
Istanbul
Country [25] 0 0
Turkey
State/province [25] 0 0
Izmir
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03853109
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03853109