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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/NCT05094336




Registration number
NCT05094336
Ethics application status
Date submitted
14/10/2021
Date registered
26/10/2021
Date last updated
9/05/2024

Titles & IDs
Public title
AMG 193, Methylthioadenosine (MTA) Cooperative Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, Alone and in Combination With Docetaxel in Advanced Methylthioadenosine Phosphorylase (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
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 escalating doses of AMG 193 and a dose of a comparator AMG 193 test tablet.

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.


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 Stable Disease (SD)
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).

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.

- Part 1i: Enrollment criteria for Part 1i are to match the criteria of the expansion
arm from which the indication was selected.

- 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
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, unless anti-tumor therapy is a
therapy with 5 times the half-life being shorter than 28 days

- 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/Phase 2
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
12/03/2029
Actual
Sample size
Target
527
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Austria
State/province [10] 0 0
Graz
Country [11] 0 0
Austria
State/province [11] 0 0
Salzburg
Country [12] 0 0
Belgium
State/province [12] 0 0
Bruxelles
Country [13] 0 0
Belgium
State/province [13] 0 0
Edegem
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Belgium
State/province [15] 0 0
Hasselt
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
France
State/province [19] 0 0
Dijon cedex
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Villejuif
Country [22] 0 0
Germany
State/province [22] 0 0
Halle (Saale)
Country [23] 0 0
Germany
State/province [23] 0 0
Heidelberg
Country [24] 0 0
Germany
State/province [24] 0 0
Ulm
Country [25] 0 0
Germany
State/province [25] 0 0
Wuerzburg
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Hong Kong
Country [27] 0 0
Hong Kong
State/province [27] 0 0
Shatin, New Territories
Country [28] 0 0
Japan
State/province [28] 0 0
Aichi
Country [29] 0 0
Japan
State/province [29] 0 0
Chiba
Country [30] 0 0
Japan
State/province [30] 0 0
Tokyo
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seongnam-si, Gyeonggi-do
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Switzerland
State/province [33] 0 0
Bellinzona
Country [34] 0 0
Switzerland
State/province [34] 0 0
Bern
Country [35] 0 0
Switzerland
State/province [35] 0 0
Geneve 14
Country [36] 0 0
Taiwan
State/province [36] 0 0
Tainan
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taipei
Country [38] 0 0
Taiwan
State/province [38] 0 0
Taoyuan
Country [39] 0 0
United Kingdom
State/province [39] 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 Parts 1 and 2 of this study is to evaluate the safety, tolerability,
and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG
193 alone and in combination with docetaxel in adult participants with metastatic or locally
advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.

The primary objective of Part 3 of this study is to evaluate the objective response rate
(ORR) of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid
tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05094336
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05094336