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Phase 2 Completed N=202 Randomized Double-blind Treatment

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

Source: ClinicalTrials.gov NCT02924883 ↗
Enrolled (actual)
202
Serious AEs
34.0%
Results posted
Feb 2019
Primary outcomePrimary: Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) — 6.8; 8.2 months — p=0.3332

Summary

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
6.8; 8.2 0.3332
PRIMARY
Percentage of Participants With Adverse Events
97.0; 99.2
SECONDARY
Overall Survival (OS)
NA; NA 0.2934
SECONDARY
Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1
43.5; 45.5
SECONDARY
Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1
NA; NA 0.6099
SECONDARY
Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine
63.9; 73.2
SECONDARY
Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)
3.19; 4.21
SECONDARY
Cmax of Total Trastuzumab
86.5; 79.5
SECONDARY
Cmax of Atezolizumab
626
SECONDARY
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab
18.3
SECONDARY
Percentage of Participants With ATAs to Trastuzumab Emtansine
0; 2.3

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 BC as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization 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 BC
  • 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/metastatic BC 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 Performance Status of 0 or 1
  • Negative serum pregnancy test within 7 days of enrollment 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 agonists, anti-programmed death-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; 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
  • Participants with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • 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
  • Leptomeningeal disease
  • History of autoimmune 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 medi
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02924883). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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