HER2 Expressing Breast or Gastric/Stomach CancersPhase 1MEDI4276NCT02576548
A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors.
A Phase 1 study testing MEDI4276 in people with HER2 Expressing Breast or Gastric/Stomach Cancers, run by MedImmune LLC at 5 sites in United States.
Trial summary
This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- HER2 Expressing Breast or Gastric/Stomach Cancers
- What is being tested?
- MEDI4276
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 5 sitesUnited States
- Study dates
- 23 Sep 2015to 23 May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Research Site
Charlotte, North Carolina, 28204
Research Site
Indianapolis, Indiana, 46202
Research Site
Nashville, Tennessee, 37203
Research Site
Sarasota, Florida, 34232
Research Site
Stanford, California, 94305
About this study
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
This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer.
- Being tested
- MEDI4276
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4276Biological
MEDI4276 is an investigational product
| Study group | Role | What they receive |
|---|---|---|
| MEDI4276 0.05 mg/kg | Experimental | Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.1 mg/kg | Experimental | Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.2 mg/kg | Experimental | Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.3 mg/kg | Experimental | Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.4 mg/kg | Experimental | Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.5 mg/kg | Experimental | Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.6 mg/kg | Experimental | Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.75 mg/kg | Experimental | Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
| MEDI4276 0.9 mg/kg | Experimental | Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. Receives: Biological: MEDI4276 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Time of informed consent through 90 days after last dose of MEDI4276
Secondary outcomes (5)
Objective Response Rate (ORR)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR
Measured: Time from Informed Consent up to 3 years
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)
Measured: From first dose of MEDI4276 thorugh to 30 days after last dose of investigational product
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.
Measured: Estimated to be from time of informed consent up to 3 years
Overall survival (OS)
Overall survival will be determined as the time from the start of treatment with MEDI4276 until death due to any cause.
Measured: Estimated to be from time of informed consent up to 3 years
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).
Measured: From first dose of MEDI4276 through to 30 days after the last dose of investigational product
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study start23 Sep 2015
- Primary completion23 May 2018
- Study completion23 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2 Expressing Breast or Gastric/Stomach CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune LLC, Study director, Sponsor GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02576548
- Sponsor's protocol ID
- D5760C00001
- Acronym
- MEDI4276
- Status last verified
- Jun 2019
- First submitted
- 28 Sep 2015
- Last updated
- 18 Jun 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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):11. doi: 10.3390/antib8010011.
PubMed 31544817
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02576548
- Acronym / sponsor ID
- MEDI4276 / D5760C00001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 23 Sep 2015 (actual)
- Primary completion
- 23 May 2018 (actual)
- Study completion
- 23 May 2018 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| MEDI4276 0.05 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.1 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.2 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.3 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.4 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.5 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.6 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.75 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
| MEDI4276 0.9 mg/kg | Experimental | Biological: MEDI4276Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 years.
- Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.
- 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.
Key exclusion criteria (7 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI4276MEDI4276 is an investigational product | Biological | 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 |
Primary outcome
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.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: Time from Informed Consent up to 3 years
Peak Plasma Concentration (Cmax)
Time frame: From first dose of MEDI4276 thorugh to 30 days after last dose of investigational product
Progression-free survival (PFS)
Time frame: Estimated to be from time of informed consent up to 3 years
Overall survival (OS)
Time frame: Estimated to be from time of informed consent up to 3 years
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2019.
- Derived from this study: PubMed 31544817Faria 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MedImmune LLC study director
Sponsor GmbH
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEDI4276 in people with HER2 Expressing Breast or Gastric/Stomach Cancers, run by MedImmune LLC at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02576548, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2019.