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

  • End date
    Mar 31, 2025
  • participants needed
  • sponsor
    Calithera Biosciences, Inc
Updated on 15 May 2022
systemic therapy
measurable disease
neutrophil count
cancer chemotherapy
lung carcinoma
squamous non-small cell lung cancer


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.


NFE2L2 mutation status for all patients will be identified using local or central next generation sequencing (NGS) testing on archival or fresh tissue or circulating tumor deoxyribonucleic acid (ctDNA), the results of which must be reviewed and approved by the Sponsor prior to enrollment. Each group will be randomized 1:1 to one of two doses/schedules of sapanisertib. Approximately 30 NFE2L2-mutant and 20 NFE2L2-wild type patients will be enrolled. Patients will be treated with sapanisertib until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), unacceptable toxicity, withdrawal of consent, or death.

Condition Non-Small Cell Lung Cancer, Squamous Non-small-cell Lung Cancer, Squamous Non-Small Cell Neoplasm of Lung, NFE2L2 Gene Mutation
Treatment Sapanisertib
Clinical Study IdentifierNCT05275673
SponsorCalithera Biosciences, Inc
Last Modified on15 May 2022


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
Significant active cardiovascular disease
Participants who are known to be HIV-positive, unless assessed to be healthy with a low risk of AIDS-related outcomes
Known active Hepatitis B or C infection
Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of the study drug
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