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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05094336




Registration number
NCT05094336
Ethics application status
Date submitted
14/10/2021
Date registered
26/10/2021

Titles & IDs
Public title
A Study of AMG 193 in Subjects With Advanced MTAP-null Solid Tumors
Scientific title
A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors
Secondary ID [1] 0 0
2023-504363-17
Secondary ID [2] 0 0
20210023
Universal Trial Number (UTN)
Trial acronym
MTAP
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 193
Treatment: Drugs - Docetaxel
Treatment: Drugs - Comparator AMG 193 Test Tablet

Experimental: Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration - Participants with MTAP-null solid tumors will receive escalating doses of AMG 193 to estimate the MTD and/or the RP2D.

A group of these participants in the United States (US) will have the option to take part in a Drug Substance Particle Size (DSPS) assessment. These participants will receive AMG 193 at a selected dose and a dose of a comparator AMG 193 table(s).

Experimental: Part 1c, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort: MTAP-null or lost MTAP expression NSCLC.

Experimental: Part 2a, Phase 1: AMG 193 Dose Exploration + Docetaxel - Participants with MTAP-null NSCLC will receive escalating doses of AMG 193 + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination.

Experimental: Part 2b, Phase 1: AMG 193 + Docetaxel Dose Expansion - Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of AMG 193 + docetaxel.

Experimental: Part 3: AMG 193 Phase 2 - Participants with MTAP-null solid tumors will receive AMG 193.

Experimental: Part 1e, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null BTC.

Experimental: Part 1f, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort:

MTAP-null head and neck squamous cell carcinoma (HNSCC)

Experimental: Part 1g, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort:

MTAP-null pancreatic adenocarcinoma

Experimental: Part 1h, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null or lost MTAP expression solid tumors (other than lymphoma or primary brain tumor).

Experimental: Part 1i, Phase 1: AMG 193 Dose Optimization - Participants will receive a randomized dose optimization evaluation of AMG 193.

Experimental: Part 1j, Phase 1: AMG 193 DSPS Substudy (US Sites Only) - Participants will receive doses of AMG 193 and comparator AMG 193 test tables at different times in a fasted state.

Experimental: Part 1k, Phase 1: AMG 193 Food Effect Substudy (US Sites Only) - Participants will receive AMG 193 once on a fasted state and once after eating a standardized high-fat, high calorie meal.

Experimental: Part 1l, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null esophageal/gastric cancer.

Experimental: Part 1m, Phase 1: AMG 193 Monotherapy Dose Expansion - Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null glioma.


Treatment: Drugs: AMG 193
AMG 193: Orally via tablet

Treatment: Drugs: Docetaxel
Docetaxel: Intravenous infusion

Treatment: Drugs: Comparator AMG 193 Test Tablet
Comparator AMG 193 test tablet: Orally via tablet. Only participants in the DSPS group of the Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration, and Part 1j, Phase 1 arms will receive comparator AMG 193 test tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
Timepoint [2] 0 0
Up to approximately 2 years
Primary outcome [3] 0 0
Part 3: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Parts 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193
Timepoint [1] 0 0
Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)
Secondary outcome [2] 0 0
Parts 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
Timepoint [2] 0 0
Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)
Secondary outcome [3] 0 0
Parts 1 and 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193
Timepoint [3] 0 0
Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)
Secondary outcome [4] 0 0
Part 2 Only: Maximal Plasma Concentration (Cmax) of Docetaxel
Timepoint [4] 0 0
Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
Secondary outcome [5] 0 0
Part 2 Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Docetaxel
Timepoint [5] 0 0
Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
Secondary outcome [6] 0 0
Part 2 Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Docetaxel
Timepoint [6] 0 0
Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
Secondary outcome [7] 0 0
Parts 1 and 2: ORR
Timepoint [7] 0 0
Up to approximately 2 years
Secondary outcome [8] 0 0
Parts 1, 2 and 3: Disease Control Rate (DCR)
Timepoint [8] 0 0
Up to approximately 2 years
Secondary outcome [9] 0 0
Parts 1, 2 and 3: Duration of Response (DoR)
Timepoint [9] 0 0
Up to approximately 2 years
Secondary outcome [10] 0 0
Parts 1, 2 and 3: Time to Response (TTR)
Timepoint [10] 0 0
Up to approximately 2 years
Secondary outcome [11] 0 0
Parts 1, 2 and 3: Duration of Disease Control (DC)
Timepoint [11] 0 0
Up to approximately 2 years
Secondary outcome [12] 0 0
Parts 1, 2 and 3: Progression-Free Survival (PFS)
Timepoint [12] 0 0
Up to approximately 2 years
Secondary outcome [13] 0 0
Parts 1, 2 and 3: Overall Survival (OS)
Timepoint [13] 0 0
Up to approximately 2 years
Secondary outcome [14] 0 0
Part 3 Only: Number of Participants Who Experience TEAE
Timepoint [14] 0 0
Up to approximately 2 years
Secondary outcome [15] 0 0
Part 1a Only: Maximal Plasma Concentration (Cmax) of AMG 193
Timepoint [15] 0 0
Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Secondary outcome [16] 0 0
Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
Timepoint [16] 0 0
Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Secondary outcome [17] 0 0
Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193
Timepoint [17] 0 0
Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Secondary outcome [18] 0 0
Part 1a Only: Maximal Plasma Concentration (Cmax) of Comparator AMG 193 Test Tablet
Timepoint [18] 0 0
Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
Secondary outcome [19] 0 0
Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Comparator AMG 193 Test Tablet
Timepoint [19] 0 0
Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
Secondary outcome [20] 0 0
Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Comparator AMG 193 Test Tablet
Timepoint [20] 0 0
Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
Secondary outcome [21] 0 0
Part 1k Only: Cmax of AMG 193 during fasted state
Timepoint [21] 0 0
Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Secondary outcome [22] 0 0
Part 1k Only: Tmax of AMG 193 during fasted state
Timepoint [22] 0 0
Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Secondary outcome [23] 0 0
Part 1k Only: AUC of AMG 193 during fasted state
Timepoint [23] 0 0
Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Secondary outcome [24] 0 0
Part 1k Only: Cmax of AMG 193 during fed state
Timepoint [24] 0 0
Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Secondary outcome [25] 0 0
Part 1k Only: Tmax of AMG 193 during fed state
Timepoint [25] 0 0
Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Secondary outcome [26] 0 0
Part 1k Only: AUC of AMG 193 during fed state
Timepoint [26] 0 0
Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)

Eligibility
Key inclusion criteria
* Participant has provided informed consent/assent before initiation of any study specific activities/procedures.
* Age = 18 years.
* Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null) (Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP) (null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
* Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.
* Able to swallow and retain orally (PO) administered study treatment and willing to record daily adherence to investigational product.
* Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Note: except participants enrolling to Part 1m.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

* Adequate hematopoietic function per local laboratory
* Adequate renal function per local laboratory
* Adequate glucose control per local laboratory (Part 1 only)
* Adequate liver function per local laboratory
* Adequate coagulation parameters
* Adequate pulmonary function
* Adequate cardiac function
* Minimum life expectancy of 12 weeks as per investigator judgement.
* A total of 25 slides of archived tumor tissue (formalin-fixed, paraffin-embedded [FFPE] sample collected within 5 years) or an archival block must be available.
* For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo tumor biopsy.
* For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment (archival sample acceptable if obtained with 6 months of enrollment and subject has not received any other treatment since sample was obtained) and while on treatment.
* For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sites only).

Food Effect Substudy (Part 1k): Specific Inclusion Criteria

* Subject able and willing to eat a standardized high-fat, high-caloric meal
* Subject able and willing to fast for = 6 hours

Specific Inclusion Criteria for subjects with glioma (Part 1m only)

-Disease measurable as defined per Modified Response Assessment in Neuro-Oncology Criteria 2.0 (mRANO 2.0)
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Spinal cord compression or untreated brain metastases or leptomeningeal disease.
* History of other malignancy within the past 2 years
* Any evidence of current interstitial lung disease
* Active infection
* Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection.
* History of arterial thrombosis
* Myocardial infarction and/or symptomatic congestive heart failure.
* Gastrointestinal tract disease
* History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
* History of solid organ transplant.
* Diagnosis of Congenital Short QT Syndrome.
* Major surgery
* Anti-tumor therapy within 28 days of study day 1.
* Prior treatment with an methionine adenosyltransferase 2a (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
* Prior treatment with docetaxel (Part 2 only)
* Prior irradiation to 25% of the bone marrow.
* Therapeutic or palliative radiation therapy within 2 weeks of study day 1.
* Live vaccine therapy within 4 weeks before study drug administration.
* Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
* Use of prescription medications that are known strong inducers of cytochrome P450 3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1
* Unresolved toxicity from prior anti-cancer therapy
* Currently receiving treatment in another investigational device or drug study.
* Known positive test for Human Immunodeficiency Virus (HIV).
* Positive hepatitis B surface antigen
* positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
* Female participants of childbearing potential unwilling to use protocol specified method of contraception

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
27/10/2027
Actual
Sample size
Target
649
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Epworth Healthcare - East Melbourne
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Parkville
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Dakota
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Austria
State/province [16] 0 0
Salzburg
Country [17] 0 0
Belgium
State/province [17] 0 0
Bruxelles
Country [18] 0 0
Belgium
State/province [18] 0 0
Edegem
Country [19] 0 0
Belgium
State/province [19] 0 0
Gent
Country [20] 0 0
Belgium
State/province [20] 0 0
Hasselt
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
China
State/province [24] 0 0
Chongqing
Country [25] 0 0
China
State/province [25] 0 0
Shanghai
Country [26] 0 0
France
State/province [26] 0 0
Dijon
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Villejuif
Country [29] 0 0
Germany
State/province [29] 0 0
Halle (Saale)
Country [30] 0 0
Germany
State/province [30] 0 0
Heidelberg
Country [31] 0 0
Germany
State/province [31] 0 0
Ulm
Country [32] 0 0
Germany
State/province [32] 0 0
Wuerzburg
Country [33] 0 0
Hong Kong
State/province [33] 0 0
Hong Kong
Country [34] 0 0
Hong Kong
State/province [34] 0 0
Shatin, New Territories
Country [35] 0 0
Japan
State/province [35] 0 0
Aichi
Country [36] 0 0
Japan
State/province [36] 0 0
Chiba
Country [37] 0 0
Japan
State/province [37] 0 0
Tokyo
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seongnam-si, Gyeonggi-do
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Seoul
Country [40] 0 0
Switzerland
State/province [40] 0 0
Bellinzona
Country [41] 0 0
Switzerland
State/province [41] 0 0
Bern
Country [42] 0 0
Switzerland
State/province [42] 0 0
Geneve 14
Country [43] 0 0
Switzerland
State/province [43] 0 0
Sankt Gallen
Country [44] 0 0
Switzerland
State/province [44] 0 0
Zuerich
Country [45] 0 0
Taiwan
State/province [45] 0 0
Tainan
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taoyuan
Country [48] 0 0
United Kingdom
State/province [48] 0 0
London
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Sutton

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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
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/NCT05094336