Clinical Trials /

M7824 (Anti-PD-L1/TGF-Beta TRAP) in a Window Setting in Patients With Stage II-III HER2/Neu Positive (HER2+) Breast Cancer (BC)

NCT03620201

Description:

The goal of this clinical research study is to learn if giving M7824 (MSB0011359C) to patients with Stage II or III HER2+ breast cancer who are scheduled to receive chemotherapy and have surgery as part of their standard care can change how many tumor-infiltrating lymphocytes (TILs) are near the tumor. TILs are a type of white blood cell that is related to your immune system. The safety and tolerability of M7824 will also be studied. This is an investigational study. M7824 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 20 participants will be enrolled at MD Anderson. All will take part at MD Anderson.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

    <li>Brief Title: M7824 (Anti-PD-L1/TGF-Beta TRAP) in a Window Setting in Patients With Stage II-III HER2/Neu Positive (HER2+) Breast Cancer (BC)li><li>Official Title: A Pilot Single Arm Open Label Trial Evaluating M7824 (Anti-PD-L1/TGF-Beta TRAP) in a Window Setting in Patients With Stage II-III HER2/Neu Positive (HER2+) Breast Cancer (BC)li>

Clinical Trial IDs

    <li>ORG STUDY ID: 2017-0502li><li>SECONDARY ID: NCI-2018-01184li><li>NCT ID: NCT03620201li>

Conditions

    <li>Malignant Neoplasm of Breastli>

Interventions

<td>M7824 - patients with Stage II or III HER2+ breast cancertd><td>MSB0011359Ctd><td>M7824td><td>Chemotherapytd><td/><td>M7824td>
DrugSynonymsArms

Purpose

The goal of this clinical research study is to learn if giving M7824 (MSB0011359C) to patients with Stage II or III HER2+ breast cancer who are scheduled to receive chemotherapy and have surgery as part of their standard care can change how many tumor-infiltrating lymphocytes (TILs) are near the tumor. TILs are a type of white blood cell that is related to your immune system. The safety and tolerability of M7824 will also be studied. This is an investigational study. M7824 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 20 participants will be enrolled at MD Anderson. All will take part at MD Anderson.

Trial Arms

<td>M7824td><td>Experimentaltd><td>Participants receive M7824 by vein over 1 hour on Days 1 and 15 of the study.td><td>
    <li>M7824 - patients with Stage II or III HER2+ breast cancerli><li>Chemotherapyli>
td>
NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent and any locally-required authorization (e.g., HIPAA) obtained
             from the subject prior to performing any protocol-related procedures, including
             screening evaluations

          2. Age =/> 18 years at time of study entry

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          4. Clinical Stage II-III as assessed by AJCC guidelines (8th Edition, Anatomic Staging)
             with no known metastatic disease (includes hormone receptor negative breast cancer).
             -Tumor size > 2 cm and/or lymph node positive

          5. HER2+, breast cancer as defined by ASCO-CAP guidelines: HER2/neu is defined as
             positive: IHC 3+ based on circumferential membrane staining that is complete, intense
             ISH positive based on: Single-probe average HER2 copy number =/> 6.0 signals/cell.
             Dual-probe HER2/CEP17 ratio =/> 2.0; with an average HER2 copy number =/> 4.0
             signals/cell , Dual-probe HER2/CEP17 ratio =/> 2.0; with an average HER2 , copy number
             < 4.0 signals/cell , Dual-probe HER2/CEP17 ratio < 2.0; with an average HER2 , copy
             number =/> 6.0 signals/cell , Neoadjuvant systemic therapy is planned and will include
             HER2 targeted therapy in combination with chemotherapy of physician's choice.

          6. continued #5: Adequate normal organ and marrow function as defined below: - Hemoglobin
             =/> 9 g/dL - Absolute neutrophil count (ANC) =/>1.5 x 10^9/L (=/> 1500 per mm³) -
             Platelet count =/> 100 x 10^9/L (=/> 100,000 per mm³)- Serum bilirubin </= 1.5 x
             institutional upper limit of normal (ULN). This will not apply to subjects with
             confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is
             predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will
             be allowed only upon treating physician, Principal Investigator (PI) or co-PI
             approval. -AST (SGOT)/ALT (SGPT) </= 2.5 x institutional upper limit of normal

          7. continued # 5:Serum creatinine clearance >/= 60 mL/min by the Cockcroft-Gault formula
             or by 24-hour urine collection for determination of creatinine clearance: Males:
             Creatinine clearance (mL/min) = Weight (kg) x (140 minus Age) 72 x serum creatinine
             (mg/dL) Females: Creatinine clearance (mL/min) = Weight (kg) x (140 minus Age) x0.85
             72 x serum creatinine (mg/dL)

          8. Female subjects must either be of non-reproductive potential (ie, post-menopausal by
             history: =/> 60 years old and no menses for =/>1 year without an alternative medical
             cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
             of bilateral oophorectomy) or must have a negative serum pregnancy test upon study
             entry and be using highly effective contraception (that is, methods with a failure
             rate of less than 1% per year) for both male and female subjects if the risk of
             conception exists (Note: The effects of the trial treatment on the developing human
             fetus are unknown; thus, women of childbearing potential and men must agree to use
             highly effective contraception).

          9. continued # 8:Male subjects on study must also use highly effective contraception.
             Highly effective contraception must be used 30 days prior to first trial treatment
             administration, for the duration of trial treatment, and at least for 4 months after
             stopping trial treatment. Should a woman become pregnant or suspect she is pregnant
             while she or her partner is participating in this trial, the treating physician should
             be informed immediately.

         10. Subject is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study (applies to both EMD Serono
             staff and/or staff at the study site)

          2. Participation in another clinical study with an investigational product during the
             last 1 month prior to initiation of therapy

          3. Any previous treatment with a PD-1 or PD-L1 inhibitor or CTLA-4 inhibitor

          4. History of another primary malignancy except for: -Malignancy treated with curative
             intent and with no known active disease =/>1 year before the first dose of study drug
             and of low potential risk for recurrence Adequately treated non-melanoma skin cancer
             or lentigo maligna without evidence of disease Adequately treated carcinoma in situ
             without evidence of disease eg, cervical cancer in situ

          5. Has received therapy for this current diagnosis of breast cancer including endocrine
             therapy or chemotherapy.

          6. Mean QT interval corrected for heart rate (QTc) =/> 470 ms

          7. Current or prior use of immunosuppressive medication within 28 days before the first
             dose of M7824, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid

          8. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
             the past 2 years) are not excluded.

          9. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis)

         10. History of primary immunodeficiency

         11. History of organ transplants that require immunosuppression

         12. History of hypersensitivity to M7824 or any excipient of M7824

         13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
             bleeding diatheses, known history of human immunodeficiency virus (HIV) and/or viral
             hepatitis, or psychiatric illness/social situations that would limit compliance with
             study requirements or compromise the ability of the subject to give written informed
             consent

         14. Active tuberculosis

         15. Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving M7824

         16. Female subjects who are pregnant, breast-feeding or male or female patients of
             reproductive potential who are not employing an effective method of birth control.

         17. Subjects with uncontrolled seizures.

         18. Concurrent treatment with non-permitted drugs and other interventions.

         19. Any major surgery for any reason, except diagnostic biopsy, within 4 weeks of the
             enrollment.

         20. Inflammatory breast cancer
      
<td>Maximum Eligible Age:td><td>N/Atd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>change in tumor-infiltrating lymphocytes (TIL) percentage pre and post M7824 therapytd><td>Time Frame:td><td>Assessed using core biopsy tissue obtained prior to dose 1 of study drug and repeat biopsy obtained 2 weeks after dose 2 of study drugtd><td>Safety Issue:td><td/><td>Description:td><td/>

Secondary Outcome Measures

<td>Measure:td><td>Adverse Events (AE) with M7824 Therapytd><td>Time Frame:td><td>Start of M7824 therapy up to 90 days after last dosetd><td>Safety Issue:td><td/><td>Description:td><td>AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceuticalproduct, regardless of causal relationship with this treatment. AE determined by the NCI-CTCAE v4.03.td>
<td>Measure:td><td>Pathological Response with M7824 Therapytd><td>Time Frame:td><td>56 days after completing chemotherapyatsurgerytd><td>Safety Issue:td><td/><td>Description:td><td/>

Details

<td>Phase:td><td>Early Phase 1td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Recruitingtd><td>Lead Sponsor:td><td>M.D. Anderson Cancer Centertd>

Last Updated

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