Clinical Trials /

M7824 in Treating Patients With Stage II-III HER2 Positive Breast Cancer

NCT03620201

Description:

This phase I trial studies how well anti-PD-L1/TGFbetaRII fusion protein M7824 (M7824) works in treating patients with stage II-III HER2 positive breast cancer. Immunotherapy with M7824 may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: M7824 in Treating Patients With Stage II-III HER2 Positive Breast Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 2017-0502
  • SECONDARY ID: NCI-2018-01184
  • SECONDARY ID: 2017-0502
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03620201

Conditions

  • Anatomic Stage II Breast Cancer AJCC v8
  • Anatomic Stage IIA Breast Cancer AJCC v8
  • Anatomic Stage IIB Breast Cancer AJCC v8
  • Anatomic Stage III Breast Cancer AJCC v8
  • Anatomic Stage IIIA Breast Cancer AJCC v8
  • Anatomic Stage IIIB Breast Cancer AJCC v8
  • Anatomic Stage IIIC Breast Cancer AJCC v8
  • Prognostic Stage II Breast Cancer AJCC v8
  • Prognostic Stage IIA Breast Cancer AJCC v8
  • Prognostic Stage IIB Breast Cancer AJCC v8
  • Prognostic Stage III Breast Cancer AJCC v8
  • Prognostic Stage IIIA Breast Cancer AJCC v8
  • Prognostic Stage IIIB Breast Cancer AJCC v8
  • Prognostic Stage IIIC Breast Cancer AJCC v8

Interventions

DrugSynonymsArms
Bintrafusp AlfaAnti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359CTreatment (M7824)

Purpose

This phase I trial studies how well anti-PD-L1/TGFbetaRII fusion protein M7824 (M7824) works in treating patients with stage II-III HER2 positive breast cancer. Immunotherapy with M7824 may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the change in tumor-infiltrating lymphocytes (TIL) percentage pre and post
      M7824 therapy.

      SECONDARY OBJECTIVES:

      I. To evaluate the safety and tolerability of M7824 in early stage breast cancer (stage
      II/III).

      II. To evaluate pathological response at the time of surgery after 2 doses of M7824 followed
      by neoadjuvant (human epidermal growth factor receptor 2) HER2 targeted therapy in
      combination with chemotherapy of physician's choice.

      EXPLORATORY OBJECTIVES:

      I. To evaluate imaging based response to M7824. II. To evaluate potential systemic and tumor
      based predictive biomarker candidates of response.

      III. To evaluate immune responses induced by exposure to M7824 systemically and in tumor
      microenvironment (TME).

      OUTLINE:

      Patients receive anti-PD-L1/TGFbetaRII fusion protein M7824 intravenously (IV) over 1 hour on
      days 1 and 15. During days 28-56 patients receive planned neoadjuvant chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (M7824)ExperimentalParticipants receive anti-PD-L1/TGFbetaRII fusion protein M7824 IV over 1 hour on days 1 and 15. During days 28-56 participants receive planned neoadjuvant chemotherapy.
  • Bintrafusp Alfa

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent and any locally-required authorization (e.g., Health
             Insurance Portability and Accountability Act [HIPAA]) obtained from the subject prior
             to performing any protocol-related procedures, including screening evaluations

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

          -  Tumor size >= 2 cm and with no known distant metastatic disease

          -  HER2+, breast cancer as defined by American Society of Clinical Oncology
             (ASCO)-College of American Pathologists (CAP) guidelines: HER2/neu is defined as
             positive: immunohistochemistry (IHC) 3+ based on circumferential membrane staining
             that is complete, intense in situ hybridization (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

          -  Hemoglobin >= 9 g/dL

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (>= 1500 per mm^3)

          -  Platelet count >= 100 x 10^9/L (>= 100,000 per mm^3)

          -  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

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Serum creatinine clearance >= 60 mL/min by the Cockcroft-Gault formula or by 24-hour
             urine collection for determination of creatinine clearance

          -  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). 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

          -  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:

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

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

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

          -  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

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

          -  Mean QT interval corrected for heart rate (QTc) >= 470 ms

          -  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

          -  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

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

          -  History of primary immunodeficiency

          -  History of organ transplants that require immunosuppression

          -  History of hypersensitivity to M7824 or any excipient of M7824

          -  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

          -  Active tuberculosis

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

          -  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

          -  Subjects with uncontrolled seizures

          -  Concurrent treatment with non-permitted drugs and other interventions

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

          -  Inflammatory breast cancer

          -  History of conditions associated with bleeding diatheses
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in tumor-infiltrating lymphocytes (TIL) percentage
Time Frame:Baseline up to post M7824 therapy
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

June 4, 2020