Back to resultsA Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors. (MEDI4276)
Primary Purpose
HER2 Expressing Breast or Gastric/Stomach Cancers
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MEDI4276
Sponsored by
About this trial
This is an interventional treatment trial for HER2 Expressing Breast or Gastric/Stomach Cancers
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years.
Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.
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.
For subjects with gastric cancer:
- Prior treatment with a trastuzumab containing chemotherapy regimen is required.
- HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
- At least one lesion measurable by RECIST Version 1.1.
Exclusion Criteria:
- Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276.
History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin or liposomal doxorubicin >350 mg/m².
- Epirubicin >530 mg/m².
- Mitoxantrone >90 mg/m² and idarubicin > 70 mg/m².
- 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.
- 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.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
MEDI4276 0.05 mg/kg
MEDI4276 0.1 mg/kg
MEDI4276 0.2 mg/kg
MEDI4276 0.3 mg/kg
MEDI4276 0.4 mg/kg
MEDI4276 0.5 mg/kg
MEDI4276 0.6 mg/kg
MEDI4276 0.75 mg/kg
MEDI4276 0.9 mg/kg
Arm Description
Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Outcomes
Primary Outcome Measures
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs) and dose-limiting (DLTs).
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.
Secondary Outcome Measures
Objective Response Rate (ORR)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR
Peak Plasma Concentration (Cmax)
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)
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)
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)
The immunogencity of MEDI 4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02576548
Brief Title
A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors.
Acronym
MEDI4276
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
September 23, 2015 (Actual)
Primary Completion Date
May 23, 2018 (Actual)
Study Completion Date
May 23, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2 Expressing Breast or Gastric/Stomach Cancers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEDI4276 0.05 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.1 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.2 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.3 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.4 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.5 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.6 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.75 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Arm Title
MEDI4276 0.9 mg/kg
Arm Type
Experimental
Arm Description
Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
Intervention Type
Biological
Intervention Name(s)
MEDI4276
Intervention Description
MEDI4276 is an investigational product
Primary Outcome Measure Information:
Title
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs) and dose-limiting (DLTs).
Description
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.
Time Frame
From Time of informed consent through 90 days after last dose of MEDI4276
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR
Time Frame
Time from Informed Consent up to 3 years
Title
Peak Plasma Concentration (Cmax)
Description
The immunogenicity of MEDI4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)
Time Frame
From first dose of MEDI4276 thorugh to 30 days after last dose of investigational product
Title
Progression-free survival (PFS)
Description
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.
Time Frame
Estimated to be from time of informed consent up to 3 years
Title
Overall survival (OS)
Description
Overall survival will be determined as the time from the start of treatment with MEDI4276 until death due to any cause.
Time Frame
Estimated to be from time of informed consent up to 3 years
Title
Area under the plasma concentration versus time curve (AUC)
Description
The immunogencity of MEDI 4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Time Frame
From first dose of MEDI4276 through to 30 days after the last dose of investigational product
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years.
Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.
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.
For subjects with gastric cancer:
Prior treatment with a trastuzumab containing chemotherapy regimen is required.
HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
At least one lesion measurable by RECIST Version 1.1.
Exclusion Criteria:
Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276.
History of exposure to the following cumulative doses of anthracyclines:
Doxorubicin or liposomal doxorubicin >350 mg/m².
Epirubicin >530 mg/m².
Mitoxantrone >90 mg/m² and idarubicin > 70 mg/m².
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Research Site
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31544817
Citation
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):11. doi: 10.3390/antib8010011.
Results Reference
derived
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A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors.
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