Clinical trial • Phase I/II • Oncology
AMG 193 for Advanced MTAP-null solid tumors | Non-small cell lung cancer | Metastatic biliary cancer | Pancreatic ductal adenocarcinoma
Phase I/II trial of AMG 193 for Advanced MTAP-null solid tumors | Non-small cell lung cancer | Metastatic biliary cancer | Pancreatic ductal adenocarcinom…
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Advanced MTAP-null solid tumors | Non-small cell lung cancer | Metastatic biliary cancer | Pancreatic ductal adenocarcinoma
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 29-07-2024
- First CTIS Authorization Date
- 22-08-2024
Trial design
Randomised, open-label, experimental arms: amg 193 monotherapy and amg 193 in combination with docetaxel; no separate active comparator or placebo arm specified. docetaxel is used in combination (dose/schedule not stated in the available record).-controlled, adaptive Phase I/II trial across 13 sites in Belgium, Germany, Austria and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Experimental arms: AMG 193 monotherapy and AMG 193 in combination with docetaxel; no separate active comparator or placebo arm specified. Docetaxel is used in combination (dose/schedule not stated in the available record).
- Adaptive
- True; design includes dose-escalation to determine MTD/RP2D (Parts 1 and 2), dose expansion cohorts, and a randomized dose optimization evaluation (Part 1i).
- Biomarker Stratified
- True; biomarker: MTAP (homozygous loss/null) and CDKN2A (homozygous loss/null)
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 556
Eligibility
Recruits 556 Subjects are adults (Age ≥ 18 years); 'isVulnerablePopulationSelected' is false. Informed consent is obtained from adult participants; Subject information and informed consent forms (Main ICF, Pre-screening ICF, Pregnancy ICF) are available (documents listed in English, French and Dutch). No assent or paediatric consent procedures are indicated..
- Vulnerable Population
- Subjects are adults (Age ≥ 18 years); 'isVulnerablePopulationSelected' is false. Informed consent is obtained from adult participants; Subject information and informed consent forms (Main ICF, Pre-screening ICF, Pregnancy ICF) are available (documents listed in English, French and Dutch). No assent or paediatric consent procedures are indicated.
Inclusion criteria
- {"criterion_text":"- Evidence of homozygous loss of CDKN2A (null) and/or MTAP (null) by NGS or central IHC\n- Adequate cardiac function.\n- Age ≥ 18 years\n- Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.\n- Able to swallow and retain PO administered study treatment and willing to record daily adherence to investigational product.\n- Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).\n- Adequate hematopoietic function.\n- Adequate renal function.\n- Adequate liver function.\n- Adequate pulmonary function."}
Exclusion criteria
- {"criterion_text":"- Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.\n- Spinal cord compression or untreated brain metastases or leptomeningeal disease.\n- Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease.\n- History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months before study entry.\n- Prior irradiation to > 25% of the bone marrow.\n- Use of prescription medications that are known strong inducers or inhibitors of CYP3A4 within 14 days or 5 half-lives before study day 1.\n- Major surgery within 28 days before first dose of AMG 193\n- Evidence of Hepatitis B or C infection"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part 1 and 2: DLTs, treatment-emergent adverse events, serious adverse events, and changes in vital signs, ECGs, and clinical laboratory tests.","definition_or_measurement_approach":"Safety endpoints measured as dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), changes in vital signs, ECGs and clinical laboratory tests (as reported in Parts 1 and 2)."}
- {"endpoint_text":"- Part 3: Objective response (defined as best overall response of confirmed CR or PR based on RECIST v1.1) derived utilizing investigator tumor assessments.","definition_or_measurement_approach":"Objective response defined as best overall response of confirmed complete response (CR) or partial response (PR) per RECIST v1.1 assessed by investigator tumor assessments."}
Secondary endpoints
- {"endpoint_text":"- Part 1 and 2: PK parameters of AMG 193 alone and in combination with docetaxel.","definition_or_measurement_approach":"Pharmacokinetic parameters (PK) of AMG 193 measured in plasma following dosing (Parts 1 and 2)."}
- {"endpoint_text":"- PK parameters of docetaxel (Parts 2a and 2b only) in combination with AMG 193 after multiple doses.","definition_or_measurement_approach":"Pharmacokinetic parameters (PK) of docetaxel measured when administered in combination with AMG 193 (Parts 2a/2b)."}
- {"endpoint_text":"- Part 1 and 2 Objective response (defined as the best overall response of confirmed CR or PR based on RECIST v1.1)","definition_or_measurement_approach":"Objective response per RECIST v1.1 (best overall response of confirmed CR or PR)."}
- {"endpoint_text":"- Disease Control (DC)","definition_or_measurement_approach":"Disease control assessed per tumor response criteria (DC as reported)."}
- {"endpoint_text":"- Duration of Response (DoR)","definition_or_measurement_approach":"Duration of Response measured from first documented response until progression or last follow-up."}
- {"endpoint_text":"- Duration of disease control (DoDC)","definition_or_measurement_approach":"Duration of disease control measured from documentation of disease control until progression or last follow-up."}
- {"endpoint_text":"- Time to Response (TTR)","definition_or_measurement_approach":"Time to Response measured from first dose to first documented response."}
- {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Overall Survival measured from date of first dose to date of death from any cause."}
- {"endpoint_text":"- Progression-Free Survival (PFS)","definition_or_measurement_approach":"Progression-Free Survival measured from date of first dose to date of progression or death per defined criteria."}
Recruitment
- Planned Sample Size
- 556
- Recruitment Window Months
- 85
- Consent Approach
- Informed consent obtained from adult participants (Age ≥ 18 years). Subject information and informed consent forms and related procedures are provided (Main ICF, Pre-screening ICF, Pregnancy ICF, and informed consent procedure documents). ICF documents are available in English, French and Dutch. No paediatric assent procedures are indicated.
Geography
- Total Number Of Sites
- 13
- Total Number Of Participants
- 98
Belgium
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 24-06-2025
- Processing Time Days
- 320
- Number Of Sites
- 5
- Number Of Participants
- 37
Sites
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Oncologie
- Principal Investigator Name
- Jean-Pascal Machiels
- Principal Investigator Email
- jean-pascal.machiels@saintluc.uclouvain.be
- Contact Person Name
- Jean-Pascal Machiels
- Contact Person Email
- jean-pascal.machiels@saintluc.uclouvain.be
- Site Name
- Jessa Ziekenhuis
- Department Name
- Respiratoire Oncologie
- Principal Investigator Name
- Kristof Cuppens
- Principal Investigator Email
- Kristof.Cuppens@jessazh.be
- Contact Person Name
- Kristof Cuppens
- Contact Person Email
- Kristof.Cuppens@jessazh.be
- Site Name
- Universiteit Gent
- Department Name
- Oncologisch centrum
- Principal Investigator Name
- Sylvie Rottey
- Principal Investigator Email
- Sylvie.Rottey@ugent.be
- Contact Person Name
- Sylvie Rottey
- Contact Person Email
- Sylvie.Rottey@ugent.be
- Site Name
- UZ Leuven
- Department Name
- Gastroenterology and Hepatology
- Principal Investigator Name
- Jeroen Dekervel
- Principal Investigator Email
- jeroen.dekervel@uzleuven.be
- Contact Person Name
- Jeroen Dekervel
- Contact Person Email
- jeroen.dekervel@uzleuven.be
- Site Name
- Antwerp University Hospital
- Department Name
- Oncologie
- Principal Investigator Name
- Hans Prenen
- Principal Investigator Email
- hans.prenen@uza.be
- Contact Person Name
- Hans Prenen
- Contact Person Email
- hans.prenen@uza.be
Germany
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 23-07-2025
- Processing Time Days
- 349
- Number Of Sites
- 2
- Number Of Participants
- 15
Sites
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- Nationales Centrum für Tumorerkrankungen (NCT)
- Principal Investigator Name
- Richard Schlenk
- Principal Investigator Email
- richard.schlenk@med.uni-heidelberg.de
- Contact Person Name
- Richard Schlenk
- Contact Person Email
- richard.schlenk@med.uni-heidelberg.de
- Site Name
- Universitaetsklinikum Wuerzburg AöR
- Department Name
- Interdisziplinäres Studienzentrum (ISZ) mit Early Clinical Trials Unit (ECTU)
- Principal Investigator Name
- Maria-Elisabeth Goebeler
- Principal Investigator Email
- isz_koordination@ukw.de
- Contact Person Name
- Maria-Elisabeth Goebeler
- Contact Person Email
- isz_koordination@ukw.de
Austria
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 22-08-2025
- Processing Time Days
- 379
- Number Of Sites
- 2
- Number Of Participants
- 16
Sites
- Site Name
- Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH
- Department Name
- University Clinic for Internal Medicine III, Clinical Department of Haematology and Oncology
- Principal Investigator Name
- Lukas Weiss
- Principal Investigator Email
- lu.weiss@salk.at
- Contact Person Name
- Lukas Weiss
- Contact Person Email
- lu.weiss@salk.at
- Site Name
- Medical University Of Graz
- Department Name
- University Hospital for Internal Medicine, Clinical Department of Oncology
- Principal Investigator Name
- Philipp Jost
- Principal Investigator Email
- philipp.jost@medunigraz.at
- Contact Person Name
- Philipp Jost
- Contact Person Email
- philipp.jost@medunigraz.at
France
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 07-01-2026
- Processing Time Days
- 517
- Number Of Sites
- 4
- Number Of Participants
- 30
Sites
- Site Name
- Institut Gustave Roussy
- Department Name
- DITEP
- Principal Investigator Name
- Sophie Postel-Vinay
- Principal Investigator Email
- sophie.postel-vinay@gustaveroussy.fr
- Contact Person Name
- Sophie Postel-Vinay
- Contact Person Email
- sophie.postel-vinay@gustaveroussy.fr
- Site Name
- Centre Georges Francois Leclerc
- Department Name
- Service Radiothérapie
- Principal Investigator Name
- Francois Ghiringhelli
- Principal Investigator Email
- fghiringhelli@cgfl.fr
- Contact Person Name
- Francois Ghiringhelli
- Contact Person Email
- fghiringhelli@cgfl.fr
- Site Name
- Hopitaux Universitaires Pitie Salpetriere
- Department Name
- Service Neuro Oncologie
- Principal Investigator Name
- Mehdi TOUAT
- Principal Investigator Email
- mehdi.touat@aphp.fr
- Contact Person Name
- Mehdi TOUAT
- Contact Person Email
- mehdi.touat@aphp.fr
- Site Name
- Centre Oscar Lambret
- Department Name
- Oncologie medicale
- Principal Investigator Name
- Loic Lebellec
- Principal Investigator Email
- l-lebellec@o-lambret.fr
- Contact Person Name
- Loic Lebellec
- Contact Person Email
- l-lebellec@o-lambret.fr
Sponsor
Primary sponsor
- Full Name
- Amgen Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Third parties
- {"country":"United States","full_name":"QPS LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"sponsorDuties codes: 1,10,11,12,13,14,15,2,3,4,5,6,7,8,9; value: Site Payments Processing/Clincard","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Personalis Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: 15; value: electrocardiogram (ECG) Vendor","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Worldcare Clinical LLC","duties_or_roles":"sponsorDuties codes: 15; value: Imaging Vendor","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Natera Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- AMG 193
- Active Substance
- AMG 193
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Combination Treatment
- Yes
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