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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 (MTAP)

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ClinicalTrials.gov Identifier: NCT05094336
Recruitment Status : Recruiting
First Posted : October 26, 2021
Last Update Posted : June 16, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

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 non-small cell lung cancer (NSCLC), after prior treatment with chemotherapy and/or a programmed death-1/ligand 1 (PD-1/L1) inhibitor.


Condition or disease Intervention/treatment Phase
Advanced MTAP-null Solid Tumors Drug: AMG 193 Drug: Docetaxel Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 1, 2022
Estimated Primary Completion Date : November 13, 2024
Estimated Study Completion Date : June 19, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: Part 1a and 1b, 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.
Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

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 squamous NSCLC.

Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

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.
Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Drug: Docetaxel
Docetaxel: Intravenous infusion

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.
Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Drug: Docetaxel
Docetaxel: Intravenous infusion

Experimental: Part 3: AMG 193 Phase 2
Participants with MTAP-null NSCLC will receive AMG 193.
Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Experimental: Part 1d, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort:

MTAP-null adenocarcinoma NSCLC

Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Experimental: Part 1e, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort:

MTAP-null cholangiocarcinoma

Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Experimental: Part 1f, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort:

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

Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Experimental: Part 1g, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort:

MTAP-null pancreatic adenocarcinoma

Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor

Experimental: Part 1h, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort:

MTAP-null solid tumor other than squamous or adenocarcinoma NSCLC, cholangiocarcinoma, HNSCC, pancreatic adenocarcinoma, primary brain tumor, and lymphoma.

Drug: AMG 193
AMG 193: Orally via tablet
Other Name: MTA Cooperative PRMT5 inhibitor




Primary Outcome Measures :
  1. Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) [ Time Frame: 28 days ]
  2. Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to approximately 2 years ]

    Adverse events (AEs) are defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests will be recorded as TEAEs.

    Serious AEs (SAEs) are defined as any event that meets at least 1 of the following serious criteria:

    • Results in death (fatal)
    • Requires in-patient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant disability/incapacity
    • Is a congenital anomaly/birth defect
    • Other medically important serious event

  3. Part 3: Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]

Secondary Outcome Measures :
  1. Parts 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193 [ Time Frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days) ]
  2. Parts 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193 [ Time Frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days) ]
  3. Parts 1 and 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193 [ Time Frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days) ]
  4. Part 2 Only: Maximal Plasma Concentration (Cmax) of Docetaxel [ Time Frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days) ]
  5. Part 2 Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Docetaxel [ Time Frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days) ]
  6. Part 2 Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Docetaxel [ Time Frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days) ]
  7. Parts 1 and 2: Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
  8. Parts 1, 2 and 3: Disease Control Rate (DCR) [ Time Frame: Up to approximately 2 years ]
  9. Parts 1, 2 and 3: Duration of Response (DoR) [ Time Frame: Up to approximately 2 years ]
  10. Parts 1, 2 and 3: Time to Response (TTR) [ Time Frame: Up to approximately 2 years ]
  11. Parts 1, 2 and 3: Duration of Stable Disease (SD) [ Time Frame: Up to approximately 2 years ]
  12. Parts 1, 2 and 3: Progression-Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
  13. Parts 1, 2 and 3: Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
  14. Part 3 Only: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to approximately 2 years ]

    Adverse events (AEs) are defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests will be recorded as TEAEs.

    Serious AEs (SAEs) are defined as any event that meets at least 1 of the following serious criteria:

    • Results in death (fatal)
    • Requires in-patient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant disability/incapacity
    • Is a congenital anomaly/birth defect
    • Other medically important serious event



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) and/or methylthioadenosine phosphorylase (MTAP) (null) or lost MTAP expression in the tumor tissue.
  • 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.
  • Tumor tissue must be available.

Exclusion Criteria:

  • Spinal cord compression or active brain metastases or leptomeningeal disease from non-brain tumors.
  • Presence of primary brain cancer.
  • Presence of hematological malignancy or lymphoma.
  • History of other malignancy within the past 2 years.
  • Evidence of lung disease.
  • Active infection.
  • History of arterial thrombosis.
  • Myocardial infarction and/or symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia.
  • Gastrointestinal tract disease.
  • History of solid organ transplant.
  • Diagnosis of Congenital Short QT Syndrome.
  • Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
  • Prior irradiation to greater than 25% of the bone marrow.
  • Unresolved toxicity from prior anti-cancer therapy.
  • Currently receiving treatment in another investigational device or drug study.
  • Known positive test for Human Immunodeficiency Virus.
  • Evidence of hepatitis B or C infection.
  • Female participants of childbearing potential with a positive pregnancy test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05094336


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
United States, Indiana
Community Health Network Recruiting
Indianapolis, Indiana, United States, 46250
United States, Maryland
American Oncology Partners of Maryland, PA Recruiting
Bethesda, Maryland, United States, 20817
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Australia, New South Wales
Chris OBrien Lifehouse Recruiting
Camperdown, New South Wales, Australia, 2050
Belgium
Universite Catholique de Louvain Cliniques Universitaires Saint Luc Recruiting
Bruxelles, Belgium, 1200
Universitair Ziekenhuis Antwerpen Recruiting
Edegem, Belgium, 2650
Universitair Ziekenhuis Gent Recruiting
Gent, Belgium, 9000
Germany
Universitaetsklinikum Halle - Saale Recruiting
Halle (Saale), Germany, 06120
Japan
Aichi Cancer Center Recruiting
Nagoya-shi, Aichi, Japan, 464-8681
National Cancer Center Hospital East Recruiting
Kashiwa-shi, Chiba, Japan, 277-8577
National Cancer Center Hospital Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT05094336    
Other Study ID Numbers: 20210023
First Posted: October 26, 2021    Key Record Dates
Last Update Posted: June 16, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 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.
Access Criteria: 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.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Metastatic MTAP-null solid tumors
Advanced MTAP-null solid tumors
Non-small cell lung cancer
NSCLC
Adenocarcinoma NSCLC
Cholangiocarcinoma
Head and neck squamous cell carcinoma
Pancreatic adenocarcinoma
Additional relevant MeSH terms:
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Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action