- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05275673
A Study of Sapanisertib in Relapsed/Refractory NFE2L2-Mutated and Wild-Type Squamous Non-Small Cell Lung Cancer
March 31, 2023 updated by: Calithera Biosciences, Inc
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
7
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Clinical Administrator
- Phone Number: 650-870-1000
- Email: clinicaltrials@calithera.com
Study Locations
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-
California
-
Davis, California, United States, 95817
- UC Davis Comprehensive Cancer Center
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Santa Rosa, California, United States, 95403
- Providence Medical Group Santa Rosa - Cancer Center
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Florida
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Fort Myers, Florida, United States, 33901
- Florida Cancer Specialists
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Ocala, Florida, United States, 34474
- Ocala Oncology Center
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Tallahassee, Florida, United States, 32308
- Florida Cancer Specialists
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Kentucky
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Louisville, Kentucky, United States, 40202
- Norton Cancer Institute, Downtown
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Michigan
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Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University - Patient Care Coordinator Center
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-
New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center - Thoracic
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Ohio
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Columbus, Ohio, United States, 43219
- Zangmeister Cancer Center
-
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Oregon
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Portland, Oregon, United States, 97213
- Providence Cancer Institute Franz Clinic
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Cancer Pavilion
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Tennessee
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Nashville, Tennessee, United States, 37203
- Tennessee Oncology
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Virginia
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Fairfax, Virginia, United States, 22031
- Virginia Cancer Specialist, PC
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 sapanisertib.
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group A - NFE2L2 Mutation, Dosing Cohort 1
sapanisertib 3 mg once daily (QD)
|
capsules for oral administration
Other Names:
|
Experimental: Group A - NFE2L2 Mutation, Dosing Cohort 2
sapanisertib 2 mg twice daily (BID)
|
capsules for oral administration
Other Names:
|
Experimental: Group B - NFE2L2 Wild-Type, Dosing Cohort 1
sapanisertib 3 mg QD
|
capsules for oral administration
Other Names:
|
Experimental: Group B - NFE2L2 Wild-Type, Dosing Cohort 2
sapanisertib 2 mg BID
|
capsules for oral administration
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
36 months
|
Number of Participants With Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs
Time Frame: after the first dose of study drug through 28 days after the last dose of sapanisertib (up to 36 months)
|
An adverse event (AE) is 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 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.
|
after the first dose of study drug through 28 days after the last dose of sapanisertib (up to 36 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of Response (DOR)
Time Frame: 36 months
|
DOR will be calculated as 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.
|
36 months
|
Progression-Free Survival (PFS)
Time Frame: 36 months
|
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.
|
36 months
|
Overall Survival (OS)
Time Frame: 36 months
|
OS is defined as the time from randomization to death due to any cause.
|
36 months
|
Overall Survival (OS) at 6 Months
Time Frame: 6 months
|
OS is defined as the time from randomization to death due to any cause.
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6 months
|
Overall Survival (OS) at 12 Months
Time Frame: 12 months
|
OS is defined as the time from randomization to death due to any cause.
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Bradley J Sumrow, MD, Calithera Biosciences, Inc
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 15, 2022
Primary Completion (Actual)
March 10, 2023
Study Completion (Actual)
March 10, 2023
Study Registration Dates
First Submitted
February 7, 2022
First Submitted That Met QC Criteria
March 2, 2022
First Posted (Actual)
March 11, 2022
Study Record Updates
Last Update Posted (Actual)
April 4, 2023
Last Update Submitted That Met QC Criteria
March 31, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CX-228-301
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
We do not plan to share the individual participant data with other researchers
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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