A Study Of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer.
This study will evaluate the efficacy and safety of ipatasertib in combination with atezolizumab and paclitaxel in locally advanced or metastatic Triple-Negative Breast Cancer (TNBC) previously untreated in this setting.
- Triple-Negative Breast Cancer
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Willingness and ability to complete all study-related assessments, including PRO assessments, in the investigator's judgement.
- Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1.
- Life expectancy of at least 6 months.
- Measurable disease according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.
- Appropriate candidate for paclitaxel monotherapy if tumor PD-L1 status is unknown or non-positive; appropriate candidate for paclitaxel and atezolizumab if tumor PD-L1 status is positive.
- Histologically documented triple-negative adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent.
- Inability to comply with study and follow-up procedures.
- History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
- Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungal agents, and anti-viral agents).
- Known HIV infection (there must be a negative HIV test at screening).
- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C.
- Current treatment with anti-viral therapy for HBV.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the study.
- Pregnancy or breastfeeding, or intention to become pregnant during the study or within 28 days after the final dose of ipatasertib/placebo, 5 months after the final dose of atezolizumab/placebo, and 6 months after the final dose of paclitaxel whichever occurs later.
- New York Heart Association Class II, III, or IV heart failure, left ventricular ejection fraction < 50%, or active ventricular arrhythmia requiring medication.
- Current unstable angina or history of myocardial infarction within 6 months prior to Day 1 of Cycle 1.
- Congenital long QT syndrome or screening QT interval corrected through use Fridericia's formula (QTcF) > 480 ms.
- Current treatment with medications used at doses known to cause clinically relevant prolongation of QT/QTc interval.
- History or presence of an abnormal ECG that is clinically significant in the investigator's opinion (including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction).
- Requirement for chronic corticosteroid therapy of > 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents for a chronic disease.
- Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high risk from treatment complications.
- History of or known presence of spinal cord metastases, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments.
- Known CNS disease, except for treated asymptomatic CNS metastases.
- Known germline BRCA1/2 deleterious mutation, unless the participant is not an appropriate candidate for a PARP-inhibitor.
- Any previous systemic therapy for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast.
- Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
- Participants who have received palliative radiotherapy to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute, reversible effects (e.g., to Grade 1 or resolved by enrolment).
- Uncontrolled pleural effusion, pericardial effusion or ascites.
- Uncontrolled tumor-related pain.
- Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer.
- Known hypersensitivity or contraindication to any component of the study treatments, including the paclitaxel excipient, macrogolglycerol ricinoleate.
- Grade >= 2 peripheral neuropathy.
- History of Type I or Type II diabetes mellitus requiring insulin.
- Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
- History of or active inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
- Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia).
- Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug.
- Prior treatment with an Akt inhibitor.
- Active or history of autoimmune disease or immune deficiency.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- Prior allogeneic stem cell or solid organ transplantation.
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with atezolizumab or within 5 months after the final dose of atezolizumab.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies.
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
- Treatment with systemic immunosuppressive medication (including, but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Double (Participant, Investigator)
Cohort 1 Arm A
|PD-L1 Non-Positive Participants receiving Paclitaxel, Atezolizumab and Ipatasertib. Participants will be randomised in a 1:1:1 ratio.||
Cohort 1 Arm B
|PD-L1 Non-Positive Participants receiving Paclitaxel, Ipatasertib and Placebo for Atezolizumab. Participants will be randomised in a 1:1:1 ratio.||
Cohort 1 Arm C
|PD-L1 Non-Positive Participants receiving Paclitaxel, Placebo for Ipatasertib and Placebo for Atezolizumab. Participants will be randomised in a 1:1:1 ratio.||
Cohort 2 Arm A
|PD-L1 Positive Participants receiving Paclitaxel, Atezolizumab and Ipatasertib. Participants will be randomised in a 1:1 ratio.||
Cohort 2 Arm B
|PD-L1 Positive Participants receiving Paclitaxel, Atezolizumab and Placebo for Ipatasertib. Participants will be randomised in a 1:1 ratio.||
- Hoffmann-La Roche
Study ContactReference Study ID: CO41101 http://www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
This study will evaluate the efficacy, safety and pharmacokinetics of ipatasertib in combination with atezolizumab and paclitaxel in locally advanced unresectable or metastatic triple-negative breast cancer (TNBC) previously untreated in this setting. Participants with Programmed Death-Ligand 1 (PD-L1) non-positive and PD-L1 positive tumors will be independently enrolled in Cohorts 1 and 2, respectively. The combination of ipatasertib, atezolizumab and paclitaxel will be evaluated in Cohorts 1 and 2 and the combination of ipatasertib and paclitaxel will be evaluated in Cohort 1.