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Estrogen Receptor NegativePhase 2NCT02536794

MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer

A Phase 2 study testing Anti-B7H1 Monoclonal Antibody MEDI4736, Laboratory Biomarker Analysis and Pharmacological Study in people with Estrogen Receptor Negative and Estrogen Receptor Positive, run by Northwestern University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The main purpose of this study is to determine the anti-tumor activity of MEDI4736 in combination with tremelimumab in patients with metastatic HER2-negative breast cancer. Both MEDI4736 and tremelimumab are antibodies (proteins used by the immune system to fight infections and cancers). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Anti-B7H1 Monoclonal Antibody MEDI4736, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesUnited States
Study dates
14 Jan 2016to 22 Jan 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a histologically documented (either primary or metastatic site) diagnosis of breast cancer that is HER2 non-overexpressing by immunohistochemistry, namely 0 or 1; if they have an equivocal immunohistochemistry, 2, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio < 2 and HER2 copy number < 4); estrogen receptor (ER) positivity is defined as 1% or greater
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Patients who are ER negative must have progressed through at least one prior chemotherapy regimen in the metastatic setting or within 12 months of their last adjuvant systemic treatment; patients who are ER positive must have progressed through standard hormone therapy options and have received at least one line of chemotherapy in the metastatic setting
  • Completion of prior chemotherapy systemic anticancer therapy at least 2 weeks prior to study entry
  • Radiation therapy must be completed at least 2 weeks prior to study entry; radiated lesions may not serve as measurable disease unless they have been radiated over 12 months prior to enrollment
  • Patients may have parenchymal brain metastases if stable (no evidence of progression) for at least 1 month after local therapy (radiation or surgery); leptomeningeal disease is excluded; must have completed any prescribed steroid taper
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  • Patients may have had a prior diagnosis of cancer if it has been > 5 years since their last treatment
  • Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 50,000/mcl
  • Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) (or =< 3 times ULN in case of liver metastasis)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 2.5 X institutional ULN (or =< 5 times ULN in case of liver metastasis)
  • Creatinine =< 2 ng/ml
  • Females of child-bearing potential (FOCBP) and males must agree to use 2 methods of adequate contraception prior to study entry, for the duration of study participation, and for number (#) days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • FOCBP must have a negative pregnancy test within 7 days prior to registration on study
  • Willingness to provide a fresh biopsy prior to study enrollment and after 2 cycles of treatment
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are not eligible.
  • Current or prior use of immunosuppressive therapy within 2 weeks of starting investigational therapy
  • Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration for at least 2 weeks; NOTE: Vitamin supplements are acceptable
  • Patients may not have received any other investigational agents within 4 weeks prior to registration
  • Prior treatment with immune therapy (including but not limited to cluster of differentiation [CD]137, OX40, programmed death [PD]-1, PD-L1 or cytotoxic T-lymphocyte antigen 4 [CTLA4] inhibitors)
  • Prior severe infusion reaction to a monoclonal antibody
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  • Patients with a history of or active autoimmune disease within the past 3 years with the following exceptions:
  • Vitiligo or alopecia
  • Hypothyroidism on stable doses of thyroid replacement therapy
  • Psoriasis not requiring systemic therapy within the past 3 years
  • History of primary immunodeficiency disease or tuberculosis
  • Major medical conditions that might affect study participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) are not eligible; other significant comorbid condition which the investigator feels might compromise effective and safe participation in the study
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
  • Uncontrolled pulmonary, renal, or hepatic dysfunction
  • Ongoing or active infection requiring systemic treatment
  • Known active or chronic viral hepatitis or human immunodeficiency virus (HIV)
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Female patients who are pregnant or nursing are not eligible

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • Northwestern University- Lake Forest Hospital

    Lake Forest, Illinois, 60045

Other trials in United States

About this study

Official title: A Single Arm Phase II Study Evaluating the Efficacy and Safety of MEDI4736 in Combination With Tremelimumab in Patients With Metastatic Her2 Negative Breast Cancer

The main purpose of this study is to determine the anti-tumor activity of MEDI4736 in combination with tremelimumab in patients with metastatic HER2-negative breast cancer. Both MEDI4736 and tremelimumab are antibodies (proteins used by the immune system to fight infections and cancers). MEDI4736 attaches to a protein in tumors called PD-L1. It may prevent cancer growth by helping certain blood cells of the immune system get rid of the tumor. Tremelimumab stimulates (wakes up) the immune system to attack the tumor by inhibiting a protein molecule called CTLA-4 on immune cells. Combining the actions of these drugs may result in better treatment options for patients with breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate clinical benefit rate in patients with metastatic HER2 negative breast cancer treated with MEDI4736 in combination with tremelimumab.

SECONDARY OBJECTIVES:

  1. To evaluate progression free survival (PFS) and overall survival (OS) in patients with metastatic HER2 negative breast cancer treated with MEDI4736 in combination with tremelimumab.

II. To evaluate safety and tolerability.

TERTIARY OBJECTIVES:

  1. To evaluate if tissue-based immunohistochemical expression of programmed death-ligand (PD-L)1; tumor infiltrating lymphocytes (TILs); peripheral T cell subpopulations; changes in tissue and peripheral T cell receptor genotype; human leukocyte antigen (HLA) genotype; and immune-related candidate gene signatures predict response to MEDI4736 in combination with tremelimumab.

II. To demonstrate the pharmacodynamic effects of MEDI4736 and tremelimumab on tissue and serum based biomarkers including PD-L1, TILs, T cell subpopulations, and T cell receptor genotype.

OUTLINE:

Patients receive MEDI4736 intravenously (IV) over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients who achieve clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) until the end of the 52 week period will then enter follow-up. During follow-up patients who develop PD may be re-treated with MEDI4736 at the dose previously administered IV for an additional 52 weeks using the same guidelines as with the initial 52 week period if they meet treatment in the setting of PD criteria. Only one 52 week retreatment period will be allowed.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and then every 6 months for 3 years.

Being tested
Anti-B7H1 Monoclonal Antibody MEDI4736, Laboratory Biomarker Analysis, Pharmacological Study, Tremelimumab
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-B7H1 Monoclonal Antibody MEDI4736Biological

    Also called MEDI4736

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • TremelimumabBiological

    Also called Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206

    Given IV

Study groups in NCT02536794
Study groupRoleWhat they receive
Treatment (MEDI4736, tremelimumab)ExperimentalPatients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.
Receives: Biological: Anti-B7H1 Monoclonal Antibody MEDI4736; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

    Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

    Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

  2. Overall Response Rate (ORR) in Patients With Triple Negative Breast Cancer (TNBC) Treated With Durvalumab in Combination With Tremelimumab

    Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

    Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    TNBC = patients whose status for ER, PR and HER2 is negative

    Measured: Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and then 1 cycle = 2 weeks for up to 45 cycles

Secondary outcomes (4)

  1. Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

    Toxicity will be evaluated by the number, frequency, and severity of adverse events as defined by the NCI Common Terminology Criteria for Adverse Events or CTCAE version 4.03

    Events that were considered to at least be possibly related to either study drugs are reported here and in general grading is as follows:

    Mild (grade 1): the event causes discomfort without disruption of normal daily activities Moderate (grade 2): the event causes discomfort that affects normal daily activities Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status Life-threatening (grade 4): the patient was at risk of death at the time of the event Fatal (grade 5): the event caused death

    Measured: Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

  2. Overall Survival (OS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

    OS is defined as the time from treatment initiation until death due to any cause

    Measured: Time from treatment initiation until 3 years post treatment continuation where patients were treated up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

  3. Progression Free Survival (PFS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

    PFS is defined as the time from treatment initiation to documented disease progression. Progressive Disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)

    Measured: Time from treatment initiation until 3 years post treatment continuation where patients were treated up to a maximum of 49 cycles where 1 cycle = 4 weeks,for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

  4. Clinical Benefit Rate (CBR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

    CBR is defined as the number of patients with complete response (CR) plus those with partial response (PR) plus those with stable disease (SD) for ≥ 12 weeks using Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

    Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Stable Disease - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study

    Measured: Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2015 (estimated)
  2. Study start14 Jan 2016
  3. Primary completion6 Feb 2020
  4. Study completion22 Jan 2021

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02536794
Sponsor's protocol ID
NU 15B01
Other IDs
NCI-2015-01445, ESR-14-10694, D4190C00030, STU00200984, NU 15B01, P30CA060553
Status last verified
Apr 2022
First submitted
28 Aug 2015
Last updated
17 May 2022
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-B7H1 Monoclonal Antibody MEDI4736, Laboratory Biomarker Analysis and Pharmacological Study in people with Estrogen Receptor Negative and Estrogen Receptor Positive, run by Northwestern University at 2 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 20 inclusion and 19 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 17 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab (time frame: Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles). The study lists 2 primary outcomes in all. 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 NCT02536794.

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 17 May 2022.

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