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A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy

NCT02924883

Description:

This Phase II, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in participants with HER2-positive locally advanced or metastatic BC who have received prior trastuzumab and taxane based therapy, either alone or in combination, and/or who have progressed within 6 months after completing adjuvant therapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab and Taxane Based Therapy
  • Official Title:

Clinical Trial IDs

  • ORG STUDY ID: WO30085
  • SECONDARY ID: 2015-004189-27
  • NCT ID: NCT02924883

Trial Conditions

  • Metastatic Breast Cancer

Trial Interventions

DrugSynonymsArms
AtezolizumabRO5541267, MPDL3280ATrastuzumab Emtansine + Atezolizumab
Trastuzumab emtansineKadcyla®, T-DM1, RO5304020Trastuzumab Emtansine + Atezolizumab

Trial Purpose

This phase II, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in participants with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab and taxane based therapy, either alone or in combination, and/or who have progressed within 6 months after completing adjuvant therapy.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab Emtansine + AtezolizumabExperimentalAtezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 of Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to approximately 28 months)
  • Atezolizumab
  • Trastuzumab emtansine
    Trastuzumab Emtansine + PlaceboActive ComparatorPlacebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 of Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to approximately 28 months)
      • Trastuzumab emtansine

      Eligibility Criteria

      Inclusion Criteria:

      - Archival tumor samples must be obtained from primary and/or metastatic sites

      - Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression

      - HER-2 positive breast cancer (BC) as defined by an immunohistochemistry (IHC) score of 3 or gene amplified by in-situ hybridization (ISH) as defined by a ratio of greater than or equal to (>/=) 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies

      - Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic breast cancer (MBC)

      - Prior treatment for BC in the: adjuvant; unresectable locally advanced; or metastatic settings; which must include both, a taxane and trastuzumab (alone or in combination with another agent)

      - Progression must have occurred during or after most recent treatment for locally advanced BC/MBC or within 6 months after completing adjuvant therapy

      - Participants must have measurable disease that is evaluable as per RECIST v1.1

      - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

      - Negative serum pregnancy test for pre-menopausal women and for women less than 12 months after the onset of menopause

      - Use of highly effective method of contraception as defined by the protocol

      Exclusion Criteria:

      - Prior treatment with trastuzumab emtansine, cluster of differentiation 137 (CD137) agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents

      - Receipt of any anti-cancer drug/biologic or investigational treatment within 28 days prior to randomization except hormone therapy, which can be given up to 7 days prior to randomization; recovery of treatment related toxicity consistent with other eligibility criteria

      - Radiation therapy within 2 weeks prior to Cycle 1, Day 1

      - History of exposure to the cumulative doses of anthracyclines

      - History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence

      - Cardiopulmonary dysfunction, symptomatic pleural effusion, pericardial effusion, or ascites

      - Current severe, uncontrolled systemic disease

      - Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment

      - Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus

      - Need for current chronic corticosteroid therapy (>/=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids)

      - Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than (>) 2 weeks prior to randomization

      - Participants with known central nervous system disease

      - History of autoimmume disease

      - Prior allogeneic stem cell or solid organ transplantation

      - Active tuberculosis

      - Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study

      - Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization

      - Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial.

      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Both
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Progression Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
      Time Frame:From Baseline until disease progression or death (up to approximately 28 months)
      Safety Issue:No
      Description:

      Secondary Outcome Measures

      Measure:Overall Survival (OS)
      Time Frame:From Baseline until death or end of study (up to approximately 28 months)
      Safety Issue:No
      Description:
      Measure:Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1
      Time Frame:From Baseline until disease progression or death (up to approximately 28 months)
      Safety Issue:No
      Description:
      Measure:Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1
      Time Frame:From Baseline until disease progression or death (up to approximately 28 months)
      Safety Issue:No
      Description:
      Measure:Percentage of Participants With Adverse Events
      Time Frame:Up to approximately 28 months
      Safety Issue:No
      Description:
      Measure:Maximum Serum Concentration of Trastuzumab Emtansine
      Time Frame:Pre-infusion(0 hour [h]),30 min after end of infusion (EOI) (over 90 min) on Day 1 of Cycle 1 and 4; pre-infusion (0 h) on Day 1 of Cycle 2(each cycle=21 days); at any time during study treatment/early discontinuation visit(up to approximately 28 months)
      Safety Issue:No
      Description:
      Measure:Serum Concentration of Total Trastuzumab
      Time Frame:Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 of Cycle 1 and 4; pre-infusion (0 h) on Day 1 of Cycle 2 (each cycle = 21 days)
      Safety Issue:No
      Description:
      Measure:Maximum Plasma Concentration of Deacetyl mercapto 1-oxopropyl maytansine (DM1)
      Time Frame:Pre-infusion (0 h) on Day 1 of Cycle 1 and 30 min after EOI (over 90 min) on Day 1 of Cycle 1 and 4 (each cycle = 21 days)
      Safety Issue:No
      Description:
      Measure:Maximum Serum Concentration of Atezolizumab
      Time Frame:Pre-infusion(0 h),30 min after EOI(over 60 min)on Day 1 of Cycle 1 & 4; pre-infusion(0 h)on Day 1 of Cycles 2,3,8 & every 8 cycles thereafter(each cycle=21 days)up to120 days after treatment completion/early discontinuation(up to approximately 28 months)
      Safety Issue:No
      Description:
      Measure:Percentage of Participants With Anti-therapeutic Antibodies (ATA) to Atezolizumab
      Time Frame:Pre-infusion (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 & every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion or early discontinuation (up to approximately 28 months)
      Safety Issue:No
      Description:
      Measure:Percentage of Participants With ATA to Trastuzumab Emtansine
      Time Frame:Pre-infusion (0 h) on Day 1 of Cycle 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (up to approximately 28 months)
      Safety Issue:No
      Description:

      Trial Keywords