Inclusion Criteria:

          -  Patients must have been assigned to S1900B based on biomarker analysis of tissue
             and/or blood and determined to have RET fusion-positive NSCLC as defined here:

               -  Patients must have RET fusion-positive NSCLC as determined by the Foundation
                  Medicine (FMI) tissue-assay, other tumor-based assays such as next-generation
                  sequencing (NGS), polymerase chain reaction (PCR), or follicular in situ
                  hybridization (FISH), or by cfDNA blood assay. Patients with RET fusions detected
                  by immunohistochemistry (IHC) alone are not eligible. The testing must be done
                  within a laboratory with Clinical Laboratory Improvement Act (CLIA),
                  International Organization for Standardization (ISO/International
                  Electrotechnical Commission (IEC), College of American Pathologists (CAP), or
                  similar certification. Presence of RET fusions detected on tests performed
                  outside of LUNGMAP must have been confirmed by the study biomarker review panel

          -  For patients whose prior therapy was for stage IV or recurrent disease, the patient
             must have received at least one line of a platinum-based chemotherapy regimen. For
             patients whose prior systemic therapy was for stage I-III disease only (i.e. patient
             has not received any treatment for stage IV or recurrent disease), disease progression
             on platinum-based chemotherapy must have occurred within one year from the last date
             that the patient received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in
             combination (e.g. nivolumab, pembrolizumab, or durvalumab) is allowed

          -  Patients must be negative for all additional validated oncogenic drivers that could
             cause resistance to LOXO-292 treatment. This includes EGFR sensitizing mutations, EGFR
             T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E
             mutation and MET exon 14 skipping mutation or high-level amplification and expression

               -  Note: EGFR, ALK, ROS, KRAS, and BRAF testing is performed as part of the LUNGMAP
                  screening/pre-screening FoundationOne test. If prior data is not available,
                  results from the FMI testing must be obtained prior to sub-study registration

          -  Patients must have measurable disease documented by computed tomography (CT) or
             magnetic resonance imaging (MRI). The CT from a combined positron emission tomography
             (PET)/CT may be used to document only non-measurable disease unless it is of
             diagnostic quality. Measurable disease must be assessed within 28 days prior to
             sub-study registration. Pleural effusions, ascites and laboratory parameters are not
             acceptable as the only evidence of disease. Non-measurable disease must be assessed
             within 42 days prior to sub-study registration. All disease must be assessed and
             documented on the Baseline Tumor Assessment Form. Patients whose only measurable
             disease is within a previous radiation therapy port must demonstrate clearly
             progressive disease (in the opinion of the treating investigator) prior to
             registration. CT and MRI scans must be submitted for central review via transfer of
             images and data (TRIAD)

          -  Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42
             days prior to sub-study registration

          -  Patients with evidence of chronic hepatitis B virus (HBV) infection must have
             undetectable HBV viral load on suppressive therapy within 28 days prior to
             registration

          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. Patients with HCV infection who are currently on treatment must have an
             undetectable HCV viral load within 28 days prior to registration

          -  Patients with known human immunodeficiency virus (HIV) infection are eligible,
             provided they are on effective anti-retroviral therapy and have undetectable viral
             load at their most recent viral load test and within 6 months prior to registration

          -  Patients must be able to swallow capsules

          -  Patients must have progressed (in the opinion of the treating physician) following the
             most recent line of therapy

          -  Patients must have recovered (=< grade 1) from any side effects of prior therapy.
             Patients must not have received any radiation therapy within 14 days prior to
             sub-study registration

          -  Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to
             sub-study registration)

          -  Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study
             registration)

          -  Serum bilirubin =< institutional upper limit of normal (IULN) (within 28 days prior to
             sub-study registration). For patients with liver metastases, bilirubin must be =< 5 x
             IULN

          -  Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN
             (within 28 days prior to sub-study registration) (if both ALT and AST are done, both
             must be =< 2 IULN). For patients with liver metastases, bilirubin and either ALT or
             AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)

          -  Serum creatinine =< the IULN or calculated creatinine clearance >= 50 mL/min using the
             following Cockcroft-Gault formula (within 28 days prior to sub-study registration)

          -  Patients must have Zubrod performance status 0-1 documented within 28 days prior to
             sub-study registration

          -  Pre-study history and physical exam must be obtained within 28 days prior to sub-study
             registration

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for five years

          -  Patients must have electrolytes and blood urea nitrogen (BUN) performed within 14 days
             prior to sub-study registration

          -  Patients must agree to have blood specimens submitted for circulating tumor DNA
             (ctDNA)

          -  Patients must also be offered participation in banking and in the correlative studies
             for collection and future use of specimens

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system

          -  Patients with impaired decision-making capacity are eligible as long as their
             neurological or psychological condition does not preclude their safe participation in
             the study (e.g., tracking pill consumption and reporting adverse events to the
             investigator)

        Exclusion Criteria:

          -  Patients must not have received any prior treatment with selective anti-RET inhibitors
             (anti-RET multikinase inhibitors are permitted)

          -  Patient must not have leptomeningeal disease, spinal cord compression or brain
             metastases unless: (1) metastases have been locally treated and have remained
             clinically controlled and asymptomatic for at least 14 days following treatment, and
             prior to registration, AND (2) patient has no residual neurological dysfunction and
             has been off corticosteroids for at least 24 hours prior to sub-study registration

          -  Patients must not have received any prior systemic therapy (systemic chemotherapy,
             immunotherapy or investigational drug) within 14 days prior to sub-study registration

          -  Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
             biologic or hormonal therapy for cancer treatment while receiving treatment on this
             study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for
             diabetes and hormone replacement therapy) is acceptable

          -  Patient must not have had a major surgery within 14 days prior to sub-study
             registration. Patient must have fully recovered from the effects of prior surgery in
             the opinion of the treating investigator

          -  Patients must not have any grade III/IV cardiac disease as defined by the New York
             Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
             limitation of physical activity or resulting in inability to carry on any physical
             activity without discomfort), unstable angina pectoris, and myocardial infarction
             within 6 months, or serious uncontrolled cardiac arrhythmia

          -  Patients must not have a QT interval by Fridericia (QTcF) > 470 msec based on the
             electrocardiogram (ECG) within 28 days prior to registration. It is suggested that a
             local cardiologist review the QTcF intervals

          -  Patients must not have any clinically significant uncontrolled systemic illness,
             including but not limited to uncontrolled infection, requiring intravenous
             antibiotics, unstable angina pectoris, myocardial infarction within the past 6 months,
             uncontrolled cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes
             mellitus

               -  Uncontrolled diabetes: Patients who have a diagnosis of diabetes must have an
                  hemoglobin (Hb) A1C < 7% within 28 days prior to registration. The same criterion
                  will be used in patients with confirmed diagnosis of diabetes mellitus who have
                  been on a stable dietary or therapeutic regimen for this condition in the last
                  three months

               -  Uncontrolled blood pressure and hypertension: All blood pressure measurements
                  within the 28 days prior to registration must be systolic blood pressure (SBP) =<
                  180 and diastolic blood pressure (DBP) =< 100. An exception can be made by a
                  healthcare provider for a patient with a single blood pressure elevation who upon
                  rechecking has a blood pressure within the parameters above

          -  Patients must not have any impairment of gastrointestinal function or gastrointestinal
             disease that may significantly alter the absorption of LOXO-292 (e.g., ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel
             resection, or active peptic ulcer disease)

          -  Patients must not be planning to receive any strong inhibitors or inducers of CYP3A4
             at least 14 days prior to sub-study registration and throughout protocol treatment

          -  Patients must not be planning to use proton pump inhibitors (PPIs) at least one week
             prior to sub-study registration and throughout protocol treatment

          -  Patients must not be pregnant or nursing. Women study patients of reproductive
             potential and fertile men study patients and their partners must abstain or use
             effective contraception (including barrier method) while receiving study treatment and
             for at least 3 months after the last dose of LOXO-292. Male study patients must agree
             not to donate sperm for 6 months after the last dose of LOXO-292. A woman is
             considered to be of "reproductive potential" if she has had menses at any time in the
             preceding 12 consecutive months. In addition to routine contraceptive methods,
             "effective contraception" also includes heterosexual celibacy and surgery intended to
             prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a
             hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any
             point a previously celibate patient chooses to become heterosexually active during the
             time period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures