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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04727554




Registration number
NCT04727554
Ethics application status
Date submitted
25/01/2021
Date registered
27/01/2021

Titles & IDs
Public title
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors
Scientific title
A Phase 1, Multicenter, Open-label, Dose Exploration and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
20190136
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 994
Treatment: Drugs - AMG 404

Experimental: Part 1a: Dose Exploration - Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Experimental: Part 1b: Dose Exploration - Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Experimental: Part 1c: Dose Exploration - Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Experimental: Part 2: Dose Expansion - Participants will be administered with the MTD or RP2D of AMG 994 identified in the dose escalation part of the study, in combination with AMG 404.


Treatment: Drugs: AMG 994
Administered as an intravenous (IV) infusion.

Treatment: Drugs: AMG 404
Administered as an intravenous (IV) infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
Up to 36 months
Primary outcome [3] 0 0
Number of Participants with Treatment-Related Adverse Events
Timepoint [3] 0 0
Up to 36 months
Primary outcome [4] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurements
Timepoint [4] 0 0
Up to 24 months
Primary outcome [5] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Results
Timepoint [5] 0 0
Up to 24 months
Primary outcome [6] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests
Timepoint [6] 0 0
Up to 30 months
Secondary outcome [1] 0 0
Objective Response (OR)
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [4] 0 0
Progression-Free Survival (PFS)
Timepoint [4] 0 0
Up to 36 months
Secondary outcome [5] 0 0
Time to Progression
Timepoint [5] 0 0
Up to 36 months
Secondary outcome [6] 0 0
Time to Subsequent Therapy
Timepoint [6] 0 0
Up to 36 months
Secondary outcome [7] 0 0
Maximum Observed Serum Concentration (Cmax) of AMG 994
Timepoint [7] 0 0
Up to 30 months
Secondary outcome [8] 0 0
Maximum Observed Serum Concentration (Cmax) of AMG 404
Timepoint [8] 0 0
Up to 30 months
Secondary outcome [9] 0 0
Minimum Observed Serum Concentration (Cmin) of AMG 994
Timepoint [9] 0 0
Up to 30 months
Secondary outcome [10] 0 0
Minimum Observed Serum Concentration (Cmin) of AMG 404
Timepoint [10] 0 0
Up to 30 months
Secondary outcome [11] 0 0
Area Under the Serum Concentration-time Curve (AUC) of AMG 994
Timepoint [11] 0 0
Up to 30 months
Secondary outcome [12] 0 0
Area Under the Serum Concentration-time Curve (AUC) of AMG 404
Timepoint [12] 0 0
Up to 30 months
Secondary outcome [13] 0 0
Half-life (t1/2) of AMG 994
Timepoint [13] 0 0
Up to 30 months
Secondary outcome [14] 0 0
Half-life (t1/2) of AMG 404
Timepoint [14] 0 0
Up to 30 months

Eligibility
Key inclusion criteria
* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
* Age = 18 years at the time of signing informed consent.
* Life expectancy of > 3 months, in the opinion of the investigator.
* Participant must have histologically or cytologically proven metastatic or locally advanced solid tumors of known MSLN expression who have relapsed after and/or are refractory to established and available therapies with known clinical benefit, for which:

* No standard systemic therapy exists; or
* Standard systemic therapy has failed or is not available.
* Dose Expansion (Part 2): Participant must have one of the following malignancies: mesothelioma, pancreatic adenocarcinoma, MSLN positive NSCLC squamous cell carcinoma or adenocarcinoma, high grade serous ovarian carcinoma.
* At least 1 measurable or evaluable lesion as defined by modified RECIST 1.1 guidelines.
* Participants must be willing to undergo a biopsy prior to enrollment and during treatment with AMG 994.
* Participants 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 central nervous system (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 non-serious CNS diseases that are asymptomatic and deemed irreversible (eg, peripheral neuropathy), 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 and has not had a seizure within 1 month prior to the screening visit.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
* Hematologic function, as follows (transfusions or growth factor support must not be administered within 7 days prior to obtaining screening labs):

* Absolute neutrophil count (ANC) = 1.5 x 109/L
* Platelet count = 75 x 109/L
* Hemoglobin = 9 g/dL
* Adequate renal laboratory assessments, as follows:

• Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation = 45 mL/min/1.73 m2
* Hepatic function, as follows:

* Total bilirubin (TBL) = 1.5 x upper limit of normal (ULN) or = 3 x ULN for participants with liver metastasis
* Aspartate transaminase (AST) = 3 x ULN or = 5 x ULN for participants with liver metastasis
* Alanine aminotransferase (ALT) = 3 x ULN or = 5 x ULN for participants with liver metastasis
* Alkaline phosphatase = 2.5 x ULN or = 5 x ULN for participants with liver metastasis
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.

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 = 3 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.
* Participants with NSCLC squamous cell carcinoma (Part 1), MSLN negative NSCLC squamous cell carcinoma (Part 2), or MSLN negative NSCLC adenocarcinoma (Part 2) once the participant has been screened for MSLN expression.
* Participants with sarcomatoid mesothelioma and small cell lung cancer will be excluded from both the Dose Exploration (Part 1) and Dose Expansion (Part 2) parts of the study.
* History of solid organ transplantation.
* Major surgery within 28 days of study day 1.

Prior/Concomitant Therapy

* Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 21 days prior to study day 1.
* Treatment with a checkpoint inhibitor within 9 weeks prior to study day 1.
* 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 > 10 mg prednisone daily or equivalent. Steroids with no minimal systemic effect (such as topical or inhalation) are permitted.

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).
* Evidence of active or radiological sequelae of 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 results for human immunodeficiency virus (HIV).
* Hepatitis B and C based on the following results:

* Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
* Negative HBsAG and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
* Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
* Active infection requiring oral or intravenous therapy.
* Active or history of any autoimmune disease or immunodeficiencies. Participants with diabetes Type 1, 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 > class II), unstable angina, or cardiac arrhythmia requiring 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 noninvasive intervention AND there is agreement to allow by both the investigator and the Amgen Medical Monitor.

* Any history of grade 3 or higher colitis, pneumonitis, or neurological toxicity OR
* Unresolved toxicities from prior checkpoint inhibitor therapy, defined as not having resolved to CTCAE v5.0 grade 1.
* Exception: - clinically stable hypothyroid status managed with hormone replacement therapy, is permitted

Other Exclusions

* Female participant is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of AMG 994 and/or AMG 404.
* Female participants of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of AMG 994 and/or AMG 404.
* Female participants of childbearing potential with a positive pregnancy test assessed at day 1 by a serum pregnancy test.
* Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 8 months after the last dose of AMG 994 and/or AMG 404.
* Male participants unwilling to abstain from donating sperm during treatment and for an additional 8 months after the last dose of AMG 994 and/or AMG 404.
* Participant has known sensitivity to any of the products or components to be administered during dosing.
* Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
* History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.

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
29/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/06/2023
Sample size
Target
Accrual to date
Final
11
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
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
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Gent
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
France
State/province [8] 0 0
Lyon
Country [9] 0 0
Germany
State/province [9] 0 0
Ulm
Country [10] 0 0
Germany
State/province [10] 0 0
Würzburg
Country [11] 0 0
Japan
State/province [11] 0 0
Chiba
Country [12] 0 0
Japan
State/province [12] 0 0
Ehime
Country [13] 0 0
Poland
State/province [13] 0 0
Warszawa
Country [14] 0 0
Spain
State/province [14] 0 0
Cataluña
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04727554