Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

Inclusion Criteria:

• Patient must have enrolled onto APEC1621SC/NCI-2017-01251/ NCT03155620 and must havebeen given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH)to APEC1621D based on the presence of an actionable mutation as defined inAPEC1621SC; note that treatment assignment may be to primary cohort A for patientswith TSC1 or TSC2 loss of function mutations or primary cohort B for patients withother PI3K/MTOR pathway mutations

• Patients accruing to dose level 1 must have a body surface area >= 0.52 m^2 at thetime of study enrollment; patients accruing to dose level 2 must have a body surfacearea >= 0.37 m^2 at the time of study enrollment; patients accruing to dose level -1must have a body surface area >= 0.75 m^2 at the time of study enrollment

• Patients must have radiographically measurable disease at the time of studyenrollment; patients with neuroblastoma who do not have measurable disease but havemetaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible;measurable disease in patients with CNS involvement is defined as any lesion that isat minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) orcomputed tomography (CT)

• Note: The following do not qualify as measurable disease:

• Malignant fluid collections (e.g., ascites, pleural effusions)

• Bone marrow infiltration except that detected by MIBG scan forneuroblastoma

• Lesions only detected by nuclear medicine studies (e.g., bone, gallium orpositron emission tomography [PET] scans) except as noted forneuroblastoma

• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)

• Previously radiated lesions that have not demonstrated clear progressionpost radiation

• Leptomeningeal lesions that do not meet the measurement requirements forResponse Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Bone lesions without an associated soft tissue mass >= 10 mm in greatestdiameter; bone lesions with an associated soft tissue mass >= 10 mm ingreatest diameter imaged by CT or MRI are considered measurable

• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16years of age; Note: neurologic deficits in patients with CNS tumors must have beenstable for at least 7 days prior to study enrollment; patients who are unable towalk because of paralysis, but who are up in a wheelchair, will be consideredambulatory for the purpose of assessing the performance score

• Patients must have fully recovered from the acute toxic effects of all prioranti-cancer therapy and must meet the following minimum duration from prioranti-cancer directed therapy prior to enrollment; if after the required timeframe,the numerical eligibility criteria are met, e.g. blood count criteria, the patientis considered to have recovered adequately

• Cytotoxic chemotherapy or other anti-cancer agents known to bemyelosuppressive; >= 21 days after the last dose of cytotoxic ormyelosuppressive chemotherapy (42 days if prior nitrosourea)

• Anti-cancer agents not known to be myelosuppressive (e.g. not associated withreduced platelet or absolute neutrophil count [ANC] counts): >= 7 days afterthe last dose of agent

• Antibodies: >= 21 days must have elapsed from infusion of last dose ofantibody, and toxicity related to prior antibody therapy must be recovered tograde =< 1

• Corticosteroids: if used to modify immune adverse events related to priortherapy, >= 14 days must have elapsed since last dose of corticosteroid

• Hematopoietic growth factors: >= 14 days after the last dose of a long-actinggrowth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor;for growth factors that have known adverse events occurring beyond 7 days afteradministration, this period must be extended beyond the time during whichadverse events are known to occur; the duration of this interval must bediscussed with the study chair and the study-assigned research coordinator

• Interleukins, interferons and cytokines (other than hematopoietic growthfactors): >= 21 days after the completion of interleukins, interferon orcytokines (other than hematopoietic growth factors)

• Stem cell Infusions (with or without total body irradiation [TBI]):

• Allogeneic (non-autologous) bone marrow or stem cell transplant, or anystem cell infusion including donor lymphocyte infusion (DLI) or boostinfusion: >= 84 days after infusion and no evidence of graft versus hostdisease (GVHD)

• Autologous stem cell infusion including boost infusion: >= 42 days

• Cellular therapy: >= 42 days after the completion of any type of cellulartherapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells,etc.)

• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 daysafter local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation

• Note: radiation may not be delivered to "measurable disease" tumor site(s)being used to follow response to subprotocol treatment

• Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I-MIBG]): >= 42 days after systemically administered radiopharmaceuticaltherapy

• Patients must not have received prior exposure to LY3023414

• Patients must not have received prior exposure to an agent specificallydirected at the PI3K/MTOR pathway (a PI3K inhibitor, an AKT inhibitor, an MTORinhibitor, including rapalogs, or a combined PI3K/MTOR inhibitor)

• For patients with solid tumors without known bone marrow involvement:

• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

• Platelet count >= 100,000/mm^3 (transfusion independent, defined as notreceiving platelet transfusions for at least 7 days prior to enrollment)

• Patients with known bone marrow metastatic disease will be eligible for studyprovided they meet the blood counts (may receive transfusions provided they are notknown to be refractory to red cell or platelet transfusions); these patients willnot be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6

• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8

• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1

• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2

• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4

• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4

• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN)for age

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)

• Serum albumin >= 2 g/dL

• Patients must have a normal blood sugar level for age; if an initial random draw (i.e. non-fasting) blood glucose value is out of range, it is acceptable to repeatthis test as a fasting draw

• Patients must have a serum triglyceride level =< 300 mg/dL and serum cholesterollevel =< 300 mg/dL; if an initial random draw (i.e. non-fasting) is out of range, itis acceptable to repeat this test as a fasting draw

• Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled

• Nervous system disorders (by Common Terminology Criteria for Adverse Events version 5.0 [CTCAE V 5.0]) resulting from prior therapy must be =< grade 2, with theexception of decreased tendon reflex (DTR); any grade of DTR is eligible

• Corrected QT (QTc) interval =< 480 milliseconds

• Patients must be able to swallow intact tablets

• All patients and/or their parents or legally authorized representatives must sign awritten informed consent; assent, when appropriate, will be obtained according toinstitutional guidelines

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study; pregnancy testsmust be obtained in girls who are post-menarchal; males or females of reproductivepotential may not participate unless they have agreed to use an effectivecontraceptive method while receiving study treatment and for 3 months after the lastdose of LY3023414

• Concomitant medications

• Corticosteroids: patients receiving corticosteroids who have not been on astable or decreasing dose of corticosteroid for at least 7 days prior toenrollment are not eligible; if used to modify immune adverse events related toprior therapy, >= 14 days must have elapsed since last dose of corticosteroid

• Investigational drugs: patients who are currently receiving anotherinvestigational drug are not eligible

• Anti-cancer agents: patients who are currently receiving other anti-canceragents are not eligible

• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,tacrolimus or other agents to prevent graft-versus-host disease post bonemarrow transplant are not eligible for this trial

• Patients who have an uncontrolled infection are not eligible

• Patients who have insulin dependent diabetes are not eligible

• Patients who have received a prior solid organ transplantation are not eligible

• Patients with subependymal giant cell astrocytomas (SEGAs) are not eligible

• Patients who in the opinion of the investigator may not be able to comply with thesafety monitoring requirements of the study are not eligible