Non-Small Cell Lung CancerPhase 2NCT05275673
A Study of Sapanisertib in Relapsed/Refractory NFE2L2-Mutated and Wild-Type Squamous Non-Small Cell Lung Cancer
A Phase 2 study testing sapanisertib in people with Non-Small Cell Lung Cancer and Squamous Non-small-cell Lung Cancer, run by Faeth Therapeutics at 14 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, Squamous Non-small-cell Lung Cancer, Squamous Non-Small Cell Neoplasm of Lung
- What is being tested?
- sapanisertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 14 sitesUnited States
- Study dates
- 21 Jul 2022to 24 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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:
- 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.
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- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Zangmeister Cancer Center
Columbus, Ohio, 43219
UC Davis Comprehensive Cancer Center
Davis, California, 95817
Karmanos Cancer Institute
Detroit, Michigan, 48201
Virginia Cancer Specialist, PC
Fairfax, Virginia, 22031
Florida Cancer Specialists
Fort Myers, Florida, 33901
Norton Cancer Institute, Downtown
Louisville, Kentucky, 40202
Tennessee Oncology
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center - Thoracic
New York, New York, 10065
Ocala Oncology Center
Ocala, Florida, 34474
UPMC Cancer Pavilion
Pittsburgh, Pennsylvania, 15232
Providence Cancer Institute Franz Clinic
Portland, Oregon, 97213
Providence Medical Group Santa Rosa - Cancer Center
Santa Rosa, California, 95403
Washington University - Patient Care Coordinator Center
St Louis, Missouri, 63110
Florida Cancer Specialists
Tallahassee, Florida, 32308
About this study
Official title: A Randomized, Open-Label Phase 2 Study of the TORC 1/2 Inhibitor Sapanisertib in Relapsed/Refractory NFE2L2 (NRF2)-Mutated and Wild-Type (WT) Squamous Non-Small Cell Lung Cancer (sqNSCLC)
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.
Read the detailed description
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.
- Conditions
- Non-Small Cell Lung Cancer, Squamous Non-small-cell Lung Cancer, Squamous Non-Small Cell Neoplasm of Lung, NFE2L2 Gene Mutation
- Being tested
- sapanisertib
- Keywords
- NSCLC, sqNSCLC, NFE2L2, Next Generation Sequencing, NGS, Mutation, Relapsed, Refractory, Squamous, NRF2, Lung Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Recurrence, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapanisertibDrug
Also called CB-228
capsules for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Group A - NFE2L2 Mutation, Dosing Cohort 1 | Experimental | sapanisertib 3 mg once daily (QD) Receives: Drug: sapanisertib |
| Group A - NFE2L2 Mutation, Dosing Cohort 2 | Experimental | sapanisertib 2 mg twice daily (BID) Receives: Drug: sapanisertib |
| Group B - NFE2L2 Wild-Type, Dosing Cohort 1 | Experimental | sapanisertib 3 mg QD Receives: Drug: sapanisertib |
| Group B - NFE2L2 Wild-Type, Dosing Cohort 2 | Experimental | sapanisertib 2 mg BID Receives: Drug: sapanisertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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)
DOR is the time between the first documentation of partial response (PR) or a complete response (CR) to the first documentation of progressive disease or death, whichever occurs first.
Measured: 36 months
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first.
Measured: 36 months
Overall Survival (OS) at 6 and 12 Months
OS is defined as the time from randomization to death due to any cause.
Measured: Months 6 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2022
- Study start21 Jul 2022
- Primary completion24 Jan 2023
- Study completion24 Jan 2023
Why it stopped: Sponsor decision - funding issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Faeth Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Paik, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05275673
- Sponsor's protocol ID
- CX-228-301
- Status last verified
- Apr 2025
- First submitted
- 7 Feb 2022
- Last updated
- 24 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share the individual participant data with other researchers
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label Phase 2 Study of the TORC 1/2 Inhibitor Sapanisertib in Relapsed/Refractory NFE2L2 (NRF2)-Mutated and Wild-Type (WT) Squamous Non-Small Cell Lung Cancer (sqNSCLC)
- ClinicalTrials.gov ID
- NCT05275673
- Acronym / sponsor ID
- CX-228-301
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision - funding issues
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Faeth TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- 24 Jan 2023 (actual)
- Study completion
- 24 Jan 2023 (actual)
- First posted
- 11 Mar 2022 (actual)
- Results
- Posted 24 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Group A - NFE2L2 Mutation, Dosing Cohort 1 | Experimental | Drug: sapanisertibsapanisertib 3 mg once daily (QD) |
| Group A - NFE2L2 Mutation, Dosing Cohort 2 | Experimental | Drug: sapanisertibsapanisertib 2 mg twice daily (BID) |
| Group B - NFE2L2 Wild-Type, Dosing Cohort 1 | Experimental | Drug: sapanisertibsapanisertib 3 mg QD |
| Group B - NFE2L2 Wild-Type, Dosing Cohort 2 | Experimental | Drug: sapanisertibsapanisertib 2 mg BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (19 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sapanisertibAlso: CB-228capsules for oral administration | Drug | 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 |
Primary outcome
Investigator-Assessed Overall Response Rate (ORR) Per RECIST v1.1.
Time frame: 36 months
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.
Number of Participants With Adverse Events (AEs), Serious AEs, and Deaths
Time frame: From the first dose through 28 days after the last dose of sapanisertib (up to a maximum of 124 days).
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).
3 secondary outcomes
Duration of Response (DOR)
Time frame: 36 months
Progression-Free Survival (PFS)
Time frame: 36 months
Overall Survival (OS) at 6 and 12 Months
Time frame: Months 6 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. We do not plan to share the individual participant data with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Paik principal investigator
Memorial Sloan Kettering Cancer Center
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sapanisertib in people with Non-Small Cell Lung Cancer and Squamous Non-small-cell Lung Cancer, run by Faeth Therapeutics at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Investigator-Assessed Overall Response Rate (ORR) Per RECIST v1.1. (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.