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Trial record 50 of 283 for:    Tumor infiltrating lymphocytes

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03620201
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : January 9, 2019
EMD Serono
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Breast Drug: M7824 - patients with Stage II or III HER2+ breast cancer Drug: Chemotherapy Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 3, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: M7824
Participants receive M7824 by vein over 1 hour on Days 1 and 15 of the study.
Drug: M7824 - patients with Stage II or III HER2+ breast cancer
M7824 1200 mg administered by vein for a total of 2 doses given once every 2 weeks to patients with stage II-III HER2+ breast cancer. The first dose given within 7 days after the pretreatment biopsy. The second dose of M7824 given 14 days days after the first dose.
Other Name: MSB0011359C

Drug: Chemotherapy
After participant's last dose of M7824, participant will receive chemotherapy during Days 28-56. Study doctor decides what type of chemotherapy to be given.

Primary Outcome Measures :
  1. change in tumor-infiltrating lymphocytes (TIL) percentage pre and post M7824 therapy [ Time Frame: Assessed using core biopsy tissue obtained prior to dose 1 of study drug and repeat biopsy obtained 2 weeks after dose 2 of study drug ]

Secondary Outcome Measures :
  1. Adverse Events (AE) with M7824 Therapy [ Time Frame: Start of M7824 therapy up to 90 days after last dose ]

    AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, regardless of causal relationship with this treatment.

    AE determined by the NCI-CTCAE v4.03.

  2. Pathological Response with M7824 Therapy [ Time Frame: 56 days after completing chemotherapy at surgery ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03620201

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Contact: Jennifer Litton, MD 713-792-2817

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United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
EMD Serono
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Principal Investigator: Jennifer Litton, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT03620201     History of Changes
Other Study ID Numbers: 2017-0502
NCI-2018-01184 ( Registry Identifier: NCI CTRP )
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases