Clinical Trial - NCT03600883

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

Recruiting

Sponsor: Amgen

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03600883

Protocol Info

Short Description: Phase 1 AMG 510 in Solid tumors with Specific KRAS Mutation
Long Description: A Phase I, 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
MGH Status: Open
Sponsor: Amgen
Disease Program: Phase I

Next Steps


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Purpose

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 Title Intervention Phase
Advanced KRAS p.G12C Mutant Solid Tumors AMG 510 Phase 1
Study Type Interventional
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

Primary Outcome Measures

Number of Participants With Abnormal Laboratory Values [Time Frame: 24 Months] [Designated as safety issue: ]

Number of subjects with clinically significant changes in vital signs. [Time Frame: 24 Months] [Designated as safety issue: ]

Number of subjects with changes on ECG. [Time Frame: 24 Months] [Designated as safety issue: ]


Secondary Outcome Measures

Plasma concentration (Cmax) [Time Frame: 24 Months] [Designated as safety issue: ]

Time to achieve Cmax (tmax) [Time Frame: 24 Months] [Designated as safety issue: ]

Area under the plasma concentration-time curve (AUC) [Time Frame: 24 Months] [Designated as safety issue: ]

Objective response rate [Time Frame: 24 months] [Designated as safety issue: ]

Duration of overall response [Time Frame: 24 Months] [Designated as safety issue: ]

Progression-free survival [Time Frame: 24 Months] [Designated as safety issue: ]

Duration of stable disease [Time Frame: 24 Months] [Designated as safety issue: ]

Estimated Enrollment: 60
Study Start Date: August 2018
Estimated Study Completion Date: April 2024
Estimated Primary Completion Date: August 2020
Arms Assigned Interventions

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.

Eligibility

Ages Eligible for Study: 100 Years-100 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03600883

Locations

  • United States, California
    • Research Site Duarte, California, United States, 91010
  • United States, Colorado
    • Research Site Denver, Colorado, United States, 80218
  • United States, Indiana
    • Research Site Indianapolis, Indiana, United States, 46202
  • United States, Michigan
    • Research Site Ann Arbor, Michigan, United States, 48109
  • United States, Missouri
    • Research Site Saint Louis, Missouri, United States, 63110-1093
  • United States, New York
    • Research Site Buffalo, New York, United States, 14263
    • Research Site New York, New York, United States, 10065
  • United States, North Carolina
    • Research Site Durham, North Carolina, United States, 27710
  • United States, Pennsylvania
    • Research Site Philadelphia, Pennsylvania, United States, 19111
  • United States, Texas
    • Research Site Houston, Texas, United States, 77030
  • United States, Washington
    • Research Site Seattle, Washington, United States, 98109
  • Australia, New South Wales
    • Research Site Randwick, New South Wales, Australia, 2031
  • Australia, South Australia
    • Research Site Woodville South, South Australia, Australia, 5011
  • Australia, Victoria
    • Research Site Melbourne, Victoria, Australia, 3000

Sponsors and Collaborators

Amgen

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03600883
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019