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.
Active, not recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Atezolizumab | RO5541267, MPDL3280A | Trastuzumab Emtansine + Atezolizumab |
| Trastuzumab emtansine | Kadcyla®, T-DM1, RO5304020 | Trastuzumab Emtansine + Atezolizumab |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Trastuzumab Emtansine + Atezolizumab | Experimental | Atezolizumab 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) |
|
| Trastuzumab Emtansine + Placebo | Active Comparator | Placebo 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) |
|
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 |
| 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: |
| 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: |
