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

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).

Study Overview

• Status: Terminated
• Conditions: HNSCC
• Intervention / Treatment: Drug: Bimiralisib

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open single arm; Bimiralisib capsules orally	Drug: Bimiralisib; Bimiralisib capsules; Other Names: PQR309, PI3K/mTOR inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Radiological tumor assessments were performed by computed tomography (CT) or magnetic resonance imaging (MRI) according to a standard protocol. ORR: comprised of all patients who achieved a confirmed partial or a confirmed complete response per RECIST 1.1	At 6 and 12 weeks after the start of therapy (± 3 days)

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Faye M Johnson, MD,PhD, MD Anderson Cancer Center Recruiting, Houston, Texas, US 77030

Publications and helpful links

General Publications

• Johnson FM, Janku F, Gouda MA, Tran HT, Kawedia JD, Schmitz D, Streefkerk H, Lee JJ, Andersen CR, Deng D, Rawal S, Shah PA, El-Naggar AK, Johnson JM, Frederick MJ. Inhibition of the Phosphatidylinositol-3 Kinase Pathway Using Bimiralisib in Loss-of-Function NOTCH1-Mutant Head and Neck Cancer. Oncologist. 2022 Dec 9;27(12):1004-e926. doi: 10.1093/oncolo/oyac185.

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2019
• Primary Completion (Actual): August 5, 2020
• Study Completion (Actual): December 9, 2020

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Head and Neck Squamous Cell Carcinoma; PI3K/mTOR Inhibitor; Notch 1 loss of function mutation; Refractory metastatic
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; MTOR Inhibitors
• Other Study ID Numbers: 2018-1003 (PQR309-009); NCI-2019-02978 (Other Identifier: NCI-CTRP Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No