Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IIA Lung Cancer AJCC v8, Stage IIB Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Stage I Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8
Conditions
Brief summary
This phase I/II trial studies the side effects of sapanisertib and nivolumab and to see how well they work in treating patients with stage I-IV non-small cell lung cancer whose disease got worse on previous PD-1/PD-L1 inhibitor therapy. Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sapanisertib and nivolumab may help to control the disease.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the toxicity of the combination of sapanisertib and nivolumab in patients with advanced non-small cell lung cancer (NSCLC) who have had disease progression on prior PD-1/PD-L1 inhibitor therapy. II. To confirm recommended phase 2 dose (RP2D) of the combination of sapanisertib and nivolumab in patients with advanced NSCLC who have had disease progression on prior PD-1/PD-L1 inhibitor therapy. III. To estimate the objective response rate of the combination of sapanisertib and nivolumab in patients with advanced NSCLC who have had disease progression on prior PD-1/PD-L1 inhibitor therapy. SECONDARY OBJECTIVES: I. To determine progression free survival (PFS) of the combination of sapanisertib and nivolumab in patients with advanced NSCLC who have had disease progression on prior PD-1/PD-L1 inhibitor therapy. II. To determine overall survival (OS) of the combination of sapanisertib and nivolumab in patients with advanced NSCLC who have had disease progression on prior PD-1/PD-L1 inhibitor therapy. III. To estimate the disease control rate of the combination of sapanisertib and nivolumab in patients with advanced NSCLC who have had disease progression on prior PD-1/PD-L1 inhibitor therapy. IV. To determine if there are drug-drug interaction (DDI) for the combination of sapanisertib and nivolumab. EXPLORATORY OBJECTIVES: I. To compare gene and protein expression in pre-treatment and on-treatment tumor samples. II. To compare gene and protein expression in tumor samples of responders and nonresponders. III. To compare immune cell infiltration and immune markers in pre-treatment and on-treatment tumor samples. IV. To compare immune cell infiltration and immune markers in tumor samples of responders and non-responders. V. To correlate clinical outcomes with tumor mutational burden and cancer gene mutations detected by molecular profiling. VI. To compare gene expression at the single-cell level in pre-treatment and on-treatment tumor samples. VII. To compare gene expression at the single-cell level in tumor samples of responders and non-responders. VIII. To compare cell-free deoxyribonucleic acid (DNA) levels in pre-treatment, on-treatment, and at progression tumor samples. OUTLINE: Patients receive sapanisertib orally (PO) once daily (QD) on days 1, 8, 15, and 22 and nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Interventions
BIOLOGICALNivolumab
Given IV
DRUGSapanisertib
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with stage IV non-small cell lung cancer with disease progression on or up to 6 months from treatment with PD-1/PD- L1 inhibitor either alone or in combination with chemotherapy and/or anti-CTLA4 inhibitor; or patients with stage I-III non-small cell lung cancer with disease recurrence up to 6 months from receiving neoadjuvant/adjuvant/consolidation PD-1/PD-L1 inhibitor * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * All immune-related adverse events (AEs) while receiving prior immunotherapy must have resolved to grade =\< 1 prior to screening for the study. Patients with endocrine immune-related AE of =\< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy * Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are women of childbearing potential (WOCBP), agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, and must agree to follow instructions for methods of contraception from the time of signing the informed consent, for the duration of treatment with nivolumab and 5 months after the last dose of nivolumab (ie 30 days \[duration of ovulatory cycle\] plus the time required for nivolumab to undergo approximately five half-lives), OR * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.) * Agree not to donate egg(s) during the course of this study or within 5 months after the last dose of nivolumab (ie 30 days \[duration of ovulatory cycle\] plus the time required for nivolumab to undergo approximately five half-lives) * Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: * Are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab and up to 7 months after the last dose of nivolumab (ie 90 days \[duration of sperm turnover\] plus the time required for nivolumab to undergo approximately five half-lives)., OR * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together) * Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L without transfusion within 1 week preceding study drug administration * Platelet count \>= 100 x 10\^9/L without transfusion within 1 week preceding study drug administration * Hemoglobin \>= 9 g/dL without transfusion within 1 week preceding study drug administration * Total bilirubin =\< 1.5 x upper limit of normal (ULN) * Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) =\< 2.5 x ULN (=\< 3 x ULN if liver metastases are present) * Clearance \>= 50 mL/min based either on Cockroft-Gault estimate or based on urine collection (12 or 24 hour) * Glycosylated hemoglobin (HbA1c) \< 7.0% * Fasting serum glucose (=\< 130 mg/dL) * Fasting triglycerides =\< 300 mg/dL * Ability to swallow oral medications * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care * Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met: * Brain metastases which have been previously treated and/or are stable on most recent brain imaging * Systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid
Exclusion criteria
* Histology other than non-small cell lung cancer * Central nervous system (CNS) metastasis that is symptomatic and uncontrolled * Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days * Presence of an EGFR, ALK, and ROS1 alteration * Current systemic anti-cancer treatment other than the study agents, including other investigational agents * Previous toxicity that led to permanent and indefinite discontinuation of prior immunotherapy * Toxicity from prior immunotherapy required the use of additional immunosuppression other than corticosteroids for management of the AE * Experienced recurrence of grade \>= 3 immune-related AE if re-challenged with immunotherapy. Patients with endocrine immune-related AE of =\< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy * Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity * Known human immunodeficiency virus infection * Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol * Concurrent malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection * Breast feeding or pregnant women * Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors * Current or prior use of immunosuppressive medication within 28 days before cycle 1 of study treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid * Active or prior documented autoimmune disease within the past 2 years * NOTE: vitiligo, alopecia, chronic skin condition that does not require systemic therapy, psoriasis not requiring systemic treatment (within the past 2 years), and hypothyroidism (if stable on hormonal therapy) are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Cycle 1 through Cycle 4 (each cycle is 28 days) | Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Objective response rate will be calculated as the number of responders divided by the number of evaluable patients along with a 90% confidence interval. The ORR by dose level will also be evaluated. |
| Incidence of dose limiting toxicity (DLT) | Cycle 1 through Cycle 4 (each cycle is 28 days) | Dose Limiting Toxicity will be measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Toxicity data will be tabulated using frequency and percentage by type, grade, and attribution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate | Cycle 1 through Cycle 4 (each cycle is 28 days) | Will be measured by RECIST v1.1. Disease control will be defined as CR/PR/SD post-cycle 4; absence of disease control will be defined as PD within 4 cycles of study treatment. |
| Progression-free survival (PFS) | From enrollment until progression or death, assessed up to 16 months | The Kaplan-Meier method will be used to estimate the distribution of PFS. Median survival time (if estimable), along with the two sided 95% confidence interval (CI) will be presented. When appropriate, univariate or multicovariate Cox proportional hazards regression will be employed to explore the significances of factors on survival. |
| Area under the plasma drug concentration-time curve (AUC) | Up to 16 months | Defined as definite integral in a plot of drug concentration in blood plasma versus time. |
| Maximum serum concentration of sapanisertib (Cmax) | Up to 16 months | — |
| Overall survival (OS) | From enrollment until death by any cause, assessed up to 16 months | The Kaplan-Meier method will be used to estimate the distribution of OS. Median survival time (if estimable), along with the two sided 95% CI will be presented. When appropriate, univariate or multicovariate Cox proportional hazards regression will be employed to explore the significances of factors on survival. |
Outcome results
None listed