Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 Loss of Function Mutations

Inclusion Criteria

• Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell Carcinoma, for which no standard curative or life prolonging therapy is available
• Available CLIA-certified sequencing results of the NOTCH gene in Head and Neck Squameous Cell Carcinoma (HNSCC) tumor material. The tumor must harbor a NOTCH1 LOF mutation as confirmed by central review (MD Anderson Cancer Center, MDACC)
• ECOG performance status of ≤ 2
• Adequate bone marrow, liver, and renal functions
• Measurable disease according to RECIST version 1.1
• Patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.

Exclusion Criteria

• Has received any anti-cancer treatment including hormonal and investigational agents within 21 days prior to first dose of bimiralisib.
• Major surgery within 28 days prior to first dose of bimiralisib or persisting side effects that have not improved to NCI-CTCAE grade 1 or better.
• Pregnant or nursing (lactating) women.
• Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus
• Has other active malignancies that require systemic treatment.
• Has a known history of HIV infection
• Any of the following cardiac abnormalities:
• History of, or current, documented congestive heart failure (New York heart association functional classification iii - iv), documented cardiomyopathy
• Symptomatic (NYHA class II or higher) left ventricular ejection fraction (LVEF) < 40% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (echo)
• Myocardial infarction ≤ 6 months prior to enrolment
• Unstable angina pectoris
• Serious uncontrolled cardiac arrhythmia
• Symptomatic pericarditis
• Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
• Patient has a history of non-compliance to medical regimen or inability to grant consent.
• Medically documented history of an active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) or ≥ CTCAE grade 3 anxiety
• History of interstitial pneumonitis or patients who require chronic oxygen supplementation.