A Study of Sapanisertib in Relapsed/Refractory NFE2L2-Mutated and Wild-Type Squamous Non-Small Cell Lung Cancer

NCT05275673 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CX-228-301
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 14

Brief Summary

This is a multicenter, randomized, open-label Phase 2 study of sapanisertib in biomarker-defined populations of sqNSCLC. Patients with NFE2L2 (the name for gene encoding the protein called NRF2)-mutated or wild-type sqNSCLC should have disease that has progressed on or after at least two prior systemic therapies for metastatic disease including platinum-doublet chemotherapy and a programmed cell death 1 ligand 1 (PD-L1) inhibitor. The study will evaluate sapanisertib monotherapy in patients with relapsed/refractory sqNSCLC as two separate groups: Group A: NFE2L2-mutated sqNSCLC and Group B: NFE2L2-WT sqNSCLC.

Conditions

Non-Small Cell Lung Cancer; Squamous Non-small-cell Lung Cancer; Squamous Non-Small Cell Neoplasm of Lung; NFE2L2 Gene Mutation

Keywords

NSCLC; sqNSCLC; NFE2L2; Next Generation Sequencing; NGS; Mutation; Relapsed; Refractory; Squamous; NRF2; Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Investigator-Assessed Overall Response Rate (ORR) Per RECIST v1.1.

  ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) according to the RECIST v1.1 criteria as assessed by the investigator.

  36 months

• Number of Participants With Adverse Events (AEs), Serious AEs, and Deaths

  An adverse event (AE) is defined as any untoward, undesired, or unplanned medical occurrence in a patient administered a medicinal product whether or not considered drug related. A serious adverse event (SAE) is defined as an AE that occurs after receiving study treatment (or after signing informed consent and before receiving study treatment if due to a protocol-mandated procedure) that either results in death, is life-threatening, requires inpatient hospitalization, results in persistent or significant disability, results in congenital anomaly or birth defect, or otherwise meets criteria as an important medical event. Events were categorized as related or not related to study drug, and event severity was graded as mild (1), moderate (2), severe (3), life-threatening (4), or fatal (5).

  From the first dose through 28 days after the last dose of sapanisertib (up to a maximum of 124 days).

Secondary Outcomes (3)

• Duration of Response (DOR)

  36 months

• Progression-Free Survival (PFS)

  36 months

• Overall Survival (OS) at 6 and 12 Months

  Months 6 and 12

Study Arms (4)

Group A - NFE2L2 Mutation, Dosing Cohort 1

EXPERIMENTAL

sapanisertib 3 mg once daily (QD)

Drug: sapanisertib

Group A - NFE2L2 Mutation, Dosing Cohort 2

EXPERIMENTAL

sapanisertib 2 mg twice daily (BID)

Drug: sapanisertib

Group B - NFE2L2 Wild-Type, Dosing Cohort 1

EXPERIMENTAL

sapanisertib 3 mg QD

Drug: sapanisertib

Group B - NFE2L2 Wild-Type, Dosing Cohort 2

EXPERIMENTAL

sapanisertib 2 mg BID

Drug: sapanisertib

Interventions

sapanisertib DRUG

capsules for oral administration

Also known as: CB-228

Group A - NFE2L2 Mutation, Dosing Cohort 1; Group A - NFE2L2 Mutation, Dosing Cohort 2; Group B - NFE2L2 Wild-Type, Dosing Cohort 1; Group B - NFE2L2 Wild-Type, Dosing Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage IV squamous NSCLC.
• Disease progression during or after prior systemic therapy for metastatic disease, which must include platinum-doublet chemotherapy and immune checkpoint inhibitor therapy (anti-PD-(L)1 +/-anti-CTLA-4), if approved and available, administered as separate lines of therapy or in combination.
• Has study-eligible mutation in NFE2L2 or wild-type NFE2L2 using NGS from a College of American Pathologists- (CAP)-accredited and/or a Clinical Laboratory Improvement Amendments- (CLIA)-certified laboratory
• Must have at least one radiographically measurable lesion per RECIST v1.1 defined as a lesion that is ≥ 10 mm in longest diameter or lymph node that is ≥ 15 mm in short axis imaged by computerized tomography (CT) scan or Magnetic Resonance Imaging (MRI).
• Target lesions situated in a previously irradiated area may be considered measurable if progression has been demonstrated subsequent to radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Adequate Organ Function Laboratory Findings: Absolute neutrophil count (ANC): ≥1,500/mm3, Hemoglobin: ≥9.0 g/dL \* Transfusions and growth factors must not be used within 2 weeks prior to randomization to meet these requirements, Platelets: ≥ 100,000/mm3, Calculated creatinine clearance (CrCl): ≥ 40mL/min, Serum total bilirubin: ≤ 1.5× upper limit of normal (ULN) OR ≤ 3 mg/dL for patients with Gilbert's disease, AST (SGOT) and ALT (SGPT): ≤ 2.5× ULN OR ≤ 5× ULN for patients with liver metastases, Fasting triglycerides: \< 300 mg/dL, Fasting serum glucose: \<160 mg/dL
• A female patient of childbearing potential must:
• Have a negative serum or urine pregnancy test within 7 days prior to the first dose of study treatment
• Agree to use acceptable methods of contraception(See Section 8.1.2) during the study and for a minimum of 14 days following the last dose of sapanisertib
• Post-menopausal females (no menses for \>1 year without an alternative medical cause) and surgically sterilized females are exempt from these requirements.
• Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential and refrain from donating sperm during the study and for a minimum of 14 days following the last dose of sapanisertib.

You may not qualify if:

• Non-squamous cell histology and mixed histology tumors with any small-cell/neuroendocrine component.
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment per investigator's discretion.
• Receipt before the first dose of study drug of any of the following:
• i. Any investigational agent within 4 weeks. ii. Chemotherapy with 3 weeks (6 weeks for nitrosoureas or mitomycin C) iii. Any radiotherapy within 2 weeks prior to randomization with the exception of palliative radiotherapy for isolated tumor lesions
• Major surgery or other anticancer therapy not previously specified within 4 weeks.
• Unable or unwilling to discontinue proton pump inhibitor (PPI) use ≥ 5 days prior to randomization.
• Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoid treatment.
• Any condition including social, psychiatric or medical (including uncontrolled significant concurrent illness) that in the opinion of the Investigator could interfere with treatment or protocol-related procedures.
• Patients who are pregnant or lactating.
• Symptomatic ascites or pleural effusion. Exception: Patients who are clinically stable following treatment for these conditions (including therapeutic thoraco-or paracentesis) are eligible.
• Refractory nausea and vomiting, uncontrolled diarrhea, malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes or other situation that may preclude adequate absorption of oral study medication.
• Infection requiring more than 5 days of parenteral antibiotics, antivirals, or antifungals within two weeks prior to randomization.
• Patients receiving systemic corticosteroids greater than prednisone 10 mg or equivalent (excluding inhalers or low-dose hormone replacement therapy) within the 7 days before treatment initiation.
• Previous intolerance to mammalian target of rapamycin (mTOR), AKT, or dual PI3K/mTOR inhibitors.
• Patients with symptomatic, active/untreated central nervous system metastasis and/or leptomeningeal disease are not eligible.

Sponsors & Collaborators

• Faeth Therapeutics: lead

Study Sites (14)

UC Davis Comprehensive Cancer Center

Davis, California, 95817, United States

Location

Providence Medical Group Santa Rosa - Cancer Center

Santa Rosa, California, 95403, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Ocala Oncology Center

Ocala, Florida, 34474, United States

Location

Florida Cancer Specialists

Tallahassee, Florida, 32308, United States

Location

Norton Cancer Institute, Downtown

Louisville, Kentucky, 40202, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University - Patient Care Coordinator Center

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center - Thoracic

New York, New York, 10065, United States

Location

Zangmeister Cancer Center

Columbus, Ohio, 43219, United States

Location

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

Location

UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Virginia Cancer Specialist, PC

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence; Lung Neoplasms

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Monitor
• Organization: Faeth Therapeutics, Inc

clinicaltrials@Faeththerapeutics.com

7084069282

Study Officials

• Paul Paik

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2 dosing schedules: 3 mg once per day (3 mg total) OR 2 mg twice per day (4 mg total) Group A: 30 participants randomized 1:1 to one of two dosing schedules Group B: approximately 20 participants randomized 1:1 to one of two dosing schedules

Study Record Dates

• First Submitted: February 7, 2022
• First Posted: March 11, 2022
• Study Start: July 21, 2022
• Primary Completion: January 24, 2023
• Study Completion: January 24, 2023
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)