A Phase II, Single-arm Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Eribulin in Pretreated Advanced Triple-negative Breast Cancer Harboring a PIK3CA Mutation

Exclusion Criteria

• •Patients who meet any of the following criteria will be excluded from study entry:
• •* Pregnancy, lactation, or intention to become pregnant during the study
• •o Women of childbearing potential (including those who have had a tubal ligation) must have a negative pregnancy test result within 14 days prior to initiation of study treatment.
• •* Metaplastic breast cancer
• •* Radiotherapy within 4 weeks before Cycle 1 Day 1
• •* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• •* Malabsorption syndrome or other condition that would interfere with enteral absorption
• •* Inability or unwillingness to swallow pills
• •* Any history of leptomeningeal disease or carcinomatous meningitis
• •* Known and untreated, or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
• •* Measurable or evaluable disease (per RECIST v1.1) outside the CNS
• •* No ongoing requirement for corticosteroids as therapy for CNS metastases, with corticosteroids discontinued for ≥ 2 weeks prior to enrollment and no ongoing symptoms attributed to CNS metastases
• •* Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
• •* The screening CNS radiographic study is ≥ 4 weeks since completion of radiotherapy
• •* No history of intracranial hemorrhage or spinal cord hemorrhage
• •* Pleural effusion, pericardial effusion, or ascites requiring drainage procedures every 14 days or more frequently
• •o Indwelling pleural or abdominal catheters may be allowed, provided the patient has adequately recovered from the procedure, is hemodynamically stable and symptomatically improved.
• •* Symptomatic hypercalcemia requiring continued use of bisphosphonate or denosumab therapy
• •o Bisphosphonate and denosumab therapy for bone metastases or osteopenia/osteoporosis is allowed.
• •* Any active infection that, in the opinion of the investigator, could impact patient safety; or serious infection requiring intravenous (IV) antibiotics within 7 days prior to Day 1 of Cycle 1
• •* Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
• •* Requirement for daily supplemental oxygen
• •* Symptomatic active lung disease that is not specifically due to underlying breast cancer, including pneumonitis
• •* Active tuberculosis
• •* History of or active inflammatory disease (e.g., Crohn's disease or ulcerative colitis), or any active bowel inflammation (including diverticulitis)
• •o Patients currently receiving immunosuppressants (e.g., sulfasalazines) are considered to have active disease and are thus ineligible.
• •* Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
• •* Prior hematopoietic stem cell or bone marrow transplantation, or radiation therapy encompassing \> 30% of marrow
• •* Unresolved toxicity \> Grade 1 from prior cancer therapy, except for:
• •* Hot flashes and alopecia (may be any grade)
• •* Peripheral neuropathy (may be up to Grade 1)
• •* Significant traumatic injury or major surgical procedure within 4 weeks prior to initiation of study treatment, or planned surgery during the study
• •* Positive HIV test at screening
• •* Clinically significant history of liver disease, including severe liver impairment (ChildPugh Class B/C), active viral or other hepatitis, current alcohol abuse, or cirrhosis
• •o Patients with active HBV infection defined as: positive HbsAg, positive HbcAb, HBV DNA \> 2000 UI/mL, and/or elevated ALT levels
• •* History of malignancy within 5 years prior to consent, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• •* History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third-degree atrioventricular heart block) or evidence of prior myocardial infarction
• •* History of or active clinically significant cardiovascular dysfunction, including the following:
• •* History of stroke or transient ischemic attack within 6 months prior to first dose of study treatment
• •* History of myocardial infarction within 6 months prior to first dose of study treatment
• •* New York Heart Association Class III or IV cardiac disease or congestive heart failure requiring medication
• •* Uncontrolled arrhythmias, history of or active ventricular arrhythmia requiring medication
• •* Coronary heart disease that is symptomatic or unstable angina
• •* Congenital long QT syndrome or QT interval corrected with Fridericia's formula (QTcF) \> 470 ms demonstrated by at least two ECGs \> 30 minutes apart, history of long or short QT syndrome, Brugada syndrome or known history of corrected QT interval prolongation, or torsades de pointes.
• •* Known allergy or hypersensitivity to any of the study drugs or any of their excipients
• •* Patients with any of the following prior treatment histories are excluded:
• •* Prior treatment with PARP inhibitors for advanced TNBC
• •* Progressed solely on endocrine therapy or HER2-targeted therapy without prior chemotherapy for advanced TNBC
• •* Treatment with investigational therapy within 28 days prior to initiation of study treatment
• •* Prior treatment with any of the PI3K, AKT, or mTOR inhibitor or with eribulin