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A Phase 1, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03600883
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:

Evaluate the safety and tolerability of AMG 510 in adult subjects with KRAS p.G12C mutant solid tumors.

Estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups.


Condition or disease Intervention/treatment Phase
Advanced KRAS p.G12C Mutant Solid Tumors Drug: AMG 510 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 510 in Subjects With Advanced Solid Tumors With a Specific KRAS Mutation
Actual Study Start Date : August 27, 2018
Estimated Primary Completion Date : August 2, 2020
Estimated Study Completion Date : April 29, 2024

Arm Intervention/treatment
Experimental: Dose Exploration Part 1
Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated with AMG 510 at the lowest planned dose level of 180 mg.
Drug: AMG 510
Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation

Experimental: Dose Expansion Part 2
Upon completing the dose exploration part of the study and depending on data obtained, dose expansion at the maximum tolerated dose determined in the escalation may proceed with three groups consisting of subjects with KRAS p.G12C mutant solid tumors Dose expansion in all three groups may be done concurrently.
Drug: AMG 510
Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation




Primary Outcome Measures :
  1. Number of Participants With Abnormal Laboratory Values [ Time Frame: 24 Months ]
  2. Number of subjects with clinically significant changes in vital signs. [ Time Frame: 24 Months ]
  3. Number of subjects with changes on ECG. [ Time Frame: 24 Months ]

Secondary Outcome Measures :
  1. Plasma concentration (Cmax) [ Time Frame: 24 Months ]
  2. Time to achieve Cmax (tmax) [ Time Frame: 24 Months ]
  3. Area under the plasma concentration-time curve (AUC) [ Time Frame: 24 Months ]
  4. Objective response rate [ Time Frame: 24 months ]
  5. Duration of overall response [ Time Frame: 24 Months ]
  6. Progression-free survival [ Time Frame: 24 Months ]
  7. Duration of stable disease [ Time Frame: 24 Months ]


Information from the National Library of Medicine

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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:

  • Men or women greater than or equal to 18 years old.
  • Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12Cmutation identified through DNA sequencing.

    • Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.

Exclusion Criteria:

  • Active brain metastases from non-brain tumors.

    -- History or presence of hematological malignancies unless curatively treated with no evidence of disease

  • Myocardial infarction within 6 months of study day 1.
  • Symptomatic congestive heart failure (New York Heart Association greater than class II)
  • Unstable angina
  • Cardiac arrhythmia requiring medication
  • Gastrointestinal (GI) tract disease causing the inability to take oral medication.
  • Active infection requiring intravenous (IV) antibiotics within 1 weeks of study enrollment (day 1)
  • Positive Hepatitis B Surface Antigen (HepBsAg) or positive Hepatitis total core antibody with negative HepBsAg
  • Detectable Hepatitis C virus
  • Known positive test for HIV
  • Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible [defined as having been present and stable for greater than 6 months] may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor)

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): NCT03600883


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

Locations
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United States, California
Research Site Recruiting
Duarte, California, United States, 91010
United States, Colorado
Research Site Recruiting
Denver, Colorado, United States, 80218
United States, Indiana
Research Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Michigan
Research Site Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110-1093
United States, New York
Research Site Recruiting
Buffalo, New York, United States, 14263
Research Site Recruiting
New York, New York, United States, 10065
United States, North Carolina
Research Site Recruiting
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
United States, Washington
Research Site Recruiting
Seattle, Washington, United States, 98109
Australia, New South Wales
Research Site Recruiting
Randwick, New South Wales, Australia, 2031
Australia, South Australia
Research Site Recruiting
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Research Site Recruiting
Melbourne, Victoria, Australia, 3000
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: NCT03600883     History of Changes
Other Study ID Numbers: 20170543
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
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 link below.
URL: https://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