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

Open-label, Single Arm, Two-stage Study, Evaluating the Efficacy and Safety of Bimiralisib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinomas (HNSCC) Harboring NOTCH1 Loss of Function (LOF) Mutations

Preclinical data and limited clinical evidence suggest that Head and Neck Squameous Cell Carcinoma tumors harboring certain mutations may respond well to PI3K/mTOR inhibition (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibition).

The current study enrolls patients with refractory and / or metastatic Head and Neck Squameous Cell Carcinoma based on the mutational status of their disease to assess the response to treatment with bimiralisib, an orally available pan-PI3K/mTOR inhibitor (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibitor).

Inclusion Criteria:

1. Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell Carcinoma, for which no standard curative or life prolonging therapy is available
2. 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)
3. ECOG performance status of ≤ 2
4. Adequate bone marrow, liver, and renal functions
5. Measurable disease according to RECIST version 1.1
6. Patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.

Exclusion Criteria:

1. Has received any anti-cancer treatment including hormonal and investigational agents within 21 days prior to first dose of bimiralisib.

2. 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.

3. Pregnant or nursing (lactating) women.

4. Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus

5. Has other active malignancies that require systemic treatment.

6. Has a known history of HIV infection

7. 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

8. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.

9. Patient has a history of non-compliance to medical regimen or inability to grant consent.

10. 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

11. History of interstitial pneumonitis or patients who require chronic oxygen supplementation.