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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/NCT04727554




Registration number
NCT04727554
Ethics application status
Date submitted
25/01/2021
Date registered
27/01/2021
Date last updated
22/09/2023

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
The primary objective of this study is to evaluate the safety, tolerability, and maximum
tolerated dose (MTD)/maximum tolerated combination dose (MTCD) or recommended phase 2 dose
(RP2D) of AMG 994 as monotherapy and AMG 994 in combination with AMG 404 in participants with
advanced solid tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04727554
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/NCT04727554