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A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors. (MEDI4276)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02576548
Recruitment Status : Completed
First Posted : October 15, 2015
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE September 28, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date June 18, 2019
Actual Study Start Date  ICMJE September 23, 2015
Actual Primary Completion Date May 23, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs) and dose-limiting (DLTs). [ Time Frame: From Time of informed consent through 90 days after last dose of MEDI4276 ]
The maximum tolerated dose/maximum administered dose will be determined by the number of participants experiencing DLTs. The safety profile will be assessed through number of participants experiencing AEs, SAEs, abnormal laboratory parameters, vital signs and electrocardiogram (ECG) results.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Objective Response Rate (ORR) [ Time Frame: Time from Informed Consent up to 3 years ]
    The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR
  • Peak Plasma Concentration (Cmax) [ Time Frame: From first dose of MEDI4276 thorugh to 30 days after last dose of investigational product ]
    The immunogenicity of MEDI4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)
  • Progression-free survival (PFS) [ Time Frame: Estimated to be from time of informed consent up to 3 years ]
    Progression-free survival will be measured from the start of treatment with MEDI4276 until the first documentation of confirmed immune-related disease progression or death due to any cause, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Estimated to be from time of informed consent up to 3 years ]
    Overall survival will be determined as the time from the start of treatment with MEDI4276 until death due to any cause.
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: From first dose of MEDI4276 through to 30 days after the last dose of investigational product ]
    The immunogencity of MEDI 4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors.
Official Title  ICMJE A Phase 1/2 Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogencity, and Antitumor Activity of MEDI4276 in Subjects With Select HER2-expressing Advanced Solid Tumors
Brief Summary This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2 Expressing Breast or Gastric/Stomach Cancers
Intervention  ICMJE Biological: MEDI4276
MEDI4276 is an investigational product
Study Arms  ICMJE
  • Experimental: MEDI4276 0.05 mg/kg
    Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.1 mg/kg
    Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.2 mg/kg
    Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.3 mg/kg
    Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.4 mg/kg
    Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.5 mg/kg
    Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.6 mg/kg
    Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.75 mg/kg
    Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
  • Experimental: MEDI4276 0.9 mg/kg
    Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
    Intervention: Biological: MEDI4276
Publications * Faria M, Peay M, Lam B, Ma E, Yuan M, Waldron M, Mylott WR Jr, Liang M, Rosenbaum AI. Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2. Antibodies (Basel). 2019 Jan 11;8(1). pii: E11. doi: 10.3390/antib8010011.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2018)
47
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2015)
120
Actual Study Completion Date  ICMJE May 23, 2018
Actual Primary Completion Date May 23, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.

    1. For subjects with breast cancer:

      • Prior treatment with trastuzumab, pertuzumab, and T-DM1, either alone or in combination, is required.
      • Subjects with a primary tumor that is hormone (estrogen, progesterone, or both) receptor-positive or receptor-negative are eligible.
      • Prior hormone therapy is allowed, but last dose must be at least 14 days prior to first dose of MEDI4276.
    2. For subjects with gastric cancer:

      • Prior treatment with a trastuzumab containing chemotherapy regimen is required.
  3. HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
  4. At least one lesion measurable by RECIST Version 1.1.

Exclusion Criteria:

  1. Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276.
  2. History of exposure to the following cumulative doses of anthracyclines:

    1. Doxorubicin or liposomal doxorubicin >350 mg/m².
    2. Epirubicin >530 mg/m².
    3. Mitoxantrone >90 mg/m² and idarubicin > 70 mg/m².
    4. If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 350 mg/m² of doxorubicin.
  3. Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery or other therapy to control symptoms from brain metastases within 2 months prior to first dose of MEDI4276.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02576548
Other Study ID Numbers  ICMJE D5760C00001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MedImmune LLC Sponsor GmbH
PRS Account MedImmune LLC
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP