Clinical Trial Information

Schema EA5191

Protocol: ECOG – EA5191

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

Eligibility:

1. Patient must be ≥ 18 years of age.
2. Patient must have pathologically confirmed non-squamous non-small cell lung carcinoma (NSCLC).
3. Patient must have Stage IV disease (includes M1a, M1b, or recurrent earlier stage disease), according to the 8th edition of the lung cancer TNM classification system.
4.   Patient must have predominant non-squamous histology (patients with NSCLC NOS are eligible). Mixed tumors will be categorized by the predominant cell type. If small cell elements are present the patient is ineligible.
5. Patient’s tumor(s) must be tested and known negative for EGFR TKI sensitizing mutations (EGFR Exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements (by FISH, NGS, or IHC) by routine CLIA-certified clinical testing methods. Negative circulating tumor DNA results alone are not acceptable. Prior testing for tumor PD-L1 status is not required.
6. Patients WITHOUT tumors with known molecular alterations in ROS1, MET, RET (see below), or must have progressed radiographically (per local investigator assessment) following one, but only one, line of platinum-based chemotherapy AND one, but only one, line of prior immunotherapy. Lines of therapy are defined by clinical or radiographic progression. Patients may have received chemotherapy and immunotherapy either concurrently or sequentially in either order. (See note in Section 3.2 for patients who received prior adjuvant chemotherapy or chemoradiation.) Patient must have received at least 2 prior doses of checkpoint inhibitor therapy in an every 2, 3, or 4 week schedule. No submission of molecular testing is required and patients may be registered for Step 0 then proceed directly to Step 1 screening.
   –OR-
   Patients with tumors with known molecular alterations in ROS1, MET, and RETmust have progressed radiographically (per local investigator clinical assessment) on atleast one line of prior chemotherapy or targeted therapy, but there is no limit on number of prior number of therapies. Reciept of prior immunotherapy is allowed but not required.
7. Patient must have measurable disease.
8. Patient must have an anticipated life expectancy greater than 3 months.
9. Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the following times prior to randomization/registration: Chemotherapy/targeted oral therapy administered in a daily or weekly schedule must be completed ≥ 1 week prior to randomization/registration. Any chemotherapy administered in an every 2 week or greater schedule must be completed ≥ 2 weeks prior to randomization/registration.  Additionally, patient should be recovered to equal to or less than grade 1 toxicities related to any prior treatment, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (as determined by the treating physician).
10. Patient must not have had any prior radiation therapy for bone metastasis within 2 weeks, or any other radiation therapy within 4 weeks prior to randomization/registration.
11. History of major surgery (within 3 months, with wound healing within 28 days, prior to randomization/registration), minor surgery (within 28 days prior to randomization/registration), other minor procedures (within 7 days prior to randomization/registration) or clinically relevant ongoing complications from prior surgery.
12. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
13. Patients with new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of study treatment.

Clinical Trial Information

Schema EA5181

Protocol: ECOG – EA5181

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

Eligibility:

1. Patient must be ≥ 18 years old.
2. Patient must have one of the following:
   • Newly diagnosed stage IIIA/B/C NSCLC (per the AJCC 8th Edition) that is unresectable and is histologically and/or cytologically confirmed.
   • Nodal recurrence after surgery for early stage NSCLC.
3. Patient must have an ECOG Performance Status of 0 or 1.
4. Body weight > 30 kg of patients.
5. Patient should have a life expectancy greater than 12 weeks.
6. Patient must have a baseline ECG obtained within 6 weeks of registration.
7. Patient must have measurable disease.
8. Patient must have pulmonary function tests (PFTs) with both FEV1 and DLCO ≥ 40% of predicted, obtained within 5 months of registration.
9. Patient should be expected to have Lung V20 of ≤ 35%.
10. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met: No prior chemotherapy or radiation was ever administered for this lung cancer. Prior curative-intent surgery was at least 90 days prior to the nodal recurrence. No prior radiation was administered to the region of study cancer that would cause overlap of treatment fields.
11. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients must not have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration.
12. Patient must not have been treated with systemic immunosuppressive medications (equivalent to > 10 mg prednisone per day) or other immunosuppressive medications within 7 days of registration. Inhaled or topical steroids and adrenal replacement steroid doses equivalent to > 10 mg prednisone per day are permitted in the absence of active autoimmune disease.

Clinical Trial Information

Schema S1900C

PROTOCOL: SWOG-S1900C

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must be assigned to S1900C. Assignment to S1900C is determined by the LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker eligibility for S1900C is based on the identification of a pathogenic somatic mutation in STK11 or STK11 bi-allelic loss on tumor.
2. Patients must have histologically or cytologically confirmed Stage IV or recurrent non-squamous, mixed squamous/non-squamous (e.g., adeno-squamous carcinoma), or non-small cell lung cancer not otherwise specified (NSCLC NOS). Patients with pure squamous cell carcinoma are not eligible.
3. Patients must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for Stage III, IV or recurrent disease.
4. Any number of additional, non-platinum-based chemotherapy or targeted therapy regimens for recurrent or metastatic disease are allowed.
5. Patients may not have received more than one line of anti-PD-1 or antiPD-L1 therapy in the Stage IV or recurrent setting. Anti-PD-1 or anti-PDL1 therapy may have been given alone or in combination with platinumbased chemotherapy, an anti-CTLA4 therapy, or other immunemodulatory therapy. Patients must have experienced disease progression>42 days following initiation (Cycle 1 Day 1) of the anti-PD-1 or anti-PD-L1 containing regimen.
6. Patients who did not receive anti-PD-1 or anti-PD-L1 therapy in combination with platinum-based chemotherapy, must have also received prior platinum-based chemotherapy and experienced disease progression >42 days following initiation (Cycle 1 Day 1) of platinum based chemotherapy.
7. Patients who received anti-PD-1 or anti-PD-L1 therapy following concurrent chemoradiation for Stage III disease as their only line of antiPD-1 or anti-PD-L1 therapy, are eligible if they experienced disease progression less than (<) 365 days from the date of initiation of anti-PD-1 or anti-PD-L1 therapy.
8. Patients who received prior adjuvant platinum-based therapy post-surgical resection for Stage I-III disease (i.e. the patient has not received platinum-based chemotherapy for Stage IV or recurrent disease) must have had disease progression during or after platinum-based chemotherapy that occurred less than (<) 365 days from the last date that the patient received that therapy.
9. Patients must be able to swallow capsules whole.
10. Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g., veliparib, olaparib, rucaparib, niraparib, talazoparib) as its primary pharmacology.
11. Patients must not be taking, nor plan to take while on protocol treatment strong Pgp inhibitors (e.g. droneradone, quinidine, ranolazine, itraconazole, ketononazole), P-gp inducers (rifampin, ritonavir, tipranavir), or strong breast cancer resistance
    protein (BCRP) inhibitors (e.g. elacridar).
12. Patients must have progressed following their most recent line of therapy.
13.   Patients must not have received prior systemic immunotherapy within 28 days prior to sub-study registration and must not have received any prior systemic therapy (including systemic chemotherapy or investigational drug) within 21 days prior to sub-study registration. 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. (See 5.2c.2 for criteria regarding therapy for CNS metastases).
14. 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.
15. 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.
16. Patients must have Zubrod performance status 0-1.

Clinical Trial Information

Schema S1900B

PROTOCOL: SWOG-S1900B (Lung Map Sub-Study)

Please Note: Below is brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must have been assigned to S1900B based on biomarker analysis of tissue and/or blood and determined to have RET fusion-positive NSCLC.
2. Patients must have RET fusion-positive NSCLC as determined by the FMI tissueassay or other tumor-based assays such as NGS, PCR, or FISH, or by cfDNA blood assay. Patients with RET fusions detected by IHC alone are not eligible. The testing must
   be done within a laboratory with CLIA, ISO/IEC, 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.
3. 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.
4. 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.
5. 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.
6. Patients must not have received any prior treatment with selective anti-RET inhibitors (anti-RET multikinase inhibitors are permitted).
7. Patients must have measurable disease.
8. Patients must be able to swallow capsules.
9. Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 14 days prior to substudy registration.
10. Patients must have progressed (in the opinion of the treating physician) following the most recent line of therapy.
11. 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.
12. 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.
13. Patients must have Zubrod performance status 0-1.

Clinical Trial Information

Schema S1800A

PROTOCOL: SWOG-S1800A (Lung Map Non-Matched Sub-Study)

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must have been assigned to S1800A by the SWOG Statistics and Data Management Center (SDMC). Patients who were screened under S1400 (legacy screening/pre-screening study) must have had prior PD-L1 testing by the Dako 22C3 PharmDx IHC assay, and must have results available for stratification purposes.
2. Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, and BRAF V600E mutation unless they have progressed following all standard of care targeted therapy.
3. Patients must not have an active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.,thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is
   allowed.
4. Patients must not have any history of primary immunodeficiency.
5. Patients must not have undergone major surgery within 28 days prior to sub-study randomization, or subcutaneous venous access device placement within 7 days prior to randomization. Any patient with postoperative bleeding complications or wound complications from a surgical procedure performed in the last two months should be excluded. The patient must not have elective or planned major surgery to be performed during the course of the clinical trial.
6. 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.
7. Patients must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for Stage III, IV or recurrent disease and at most one line of anti-PD-1 or anti-PDL1 therapy for Stage IV or recurrent disease, given alone or in combination with platinum-based chemotherapy, an anti-CTLA4 therapy, or other immunemodulatory therapy. Patients must have experienced disease progression during or after this regimen. Disease progression during or after anti-PD-1 or anti-PD-L1 therapy must have occurred more than (>) 84 days following initiation (Cycle 1 Day 1) of anti-PD-1 or PD-L1 therapy (combination or monotherapy).
8. Patients who received consolidation anti-PD-1 or anti-PD-L1 therapy following concurrent chemoradiation for Stage III disease as their only line of anti-PD-1 or anti-PD-L1 therapy, are eligible if they experienced disease progression more than (>) 84 days but less than (<) 365 days from their first date of anti-PD-1 or anti-PDL1 therapy.
9. Patients must have been exposed to platinum-based chemotherapy. Patients who did not receive platinum-based chemotherapy in combination with anti-PD-1 or anti-PD-L1 therapy must have received platinum-based chemotherapy separately and experienced disease progression during or after this regimen.
10. For patients who only received prior adjuvant platinum-based therapy post-surgical resection for Stage I-III disease (i.e. the patient has not received platinum-based chemotherapy for Stage IV or recurrent disease), disease progression on platinumbased chemotherapy must have occurred within one year from the last dose that the patient received that therapy.
11. Prior tyrosine kinase inhibitor therapy for patients with targetable alterations is allowed if criteria above is also met.
12. Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy.
13. Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to substudy randomization. Patients must have recovered (≤ Grade 1) from any side effects of prior therapy, except for alopecia. Patients must not have received any radiation therapy within 14 days prior to sub-study randomization.
14. Patients must not have received nitrosoureas or mitomycin-c within 42 days prior to sub-study randomization.
15. Patients must not have received systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within seven days prior to sub-study randomization. Inhaled or topical steroids, and
    adrenal replacement doses ≤ 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
16. 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.
17. tients must have Zubrod performance status 0-1.

Clinical Trial Information

Schema NRG LU003

PROTOCOL: NRG-LU003

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

Prior to Step 1 Registration

1. Patients must have histologically or cytologically confirmed stage IV ALK-positive nonsquamous NSCLC (includes M1a, M1b, M1c stage disease). ALK rearrangement must have been demonstrated by an FDA approved assay (Vysis FISH or Ventana IHC) or by next generation sequencing (NGS).
2. Patient must be willing and able to undergo a fresh biopsy, or if patient has had a biopsy after progression on current TKI within 3 months of study enrollment (and has continued TKI for clinical benefit per treating physician) this tissue may be used. Must have
   sufficient tissue.
3. Age ≥ 18.
4. Patient must have progressive disease as defined after one second generation ALK inhibitor, including LDK378 (ceritinib), alectinib, ensartinib, and brigatinib (may not have received more than one second-generation ALK inhibitor). Patient may have received prior crizotinib; however, the second generation ALK inhibitor received must be the last treatment given prior to study enrollment.
   Prior lorlatinib (third-generation ALK inhibitor) is not allowed.
5. Prior chemotherapy is not allowed except for one prior cycle received at the time of original diagnosis of metastatic NSCLC with no evidence of disease progression following the cycle. NOTE: prior adjuvant or neoadjuvant chemotherapy is allowed if
   last dose was received more than 12 months prior to enrollment.

Prior to Step 2 Registration

1. Patients with asymptomatic treated or untreated brain metastases are eligible. Treated brain metastases are eligible as long as patients have measurable disease outside the brain. Patients must be on a stable or decreasing dose of steroids for at least 7 days prior to step 2 registration. Anticonvulsants are allowed as long as the patient is neurologically stable and not deteriorating.
2. Patients enrolled with asymptomatic brain mets must have at least one measurable target extracranial lesion.
3. ECOG performance status 0-2.
4. Patients must be able to take oral medications (i.e. swallow whole tablets/capsules).
5.  No palliative bone RT (<10 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have completed at least 1 week prior to study entry. Whole brain RT or other palliative RT must have been
   completed at least 2 weeks prior to study entry.
6.  No prior dose of second-generation ALK inhibitor (LDK378 (ceritinib), alectinib, ensartinib) within 5 days prior to step 2 registration. Prior dose of brigatinib within 7 days prior to step 2 registration.
7. Patients must not plan to receive any other investigational agents during the course of therapy.
8. Patients with active malignancy other than ALK-positive non-squamous NSCLC within the last 2 years are excluded (note: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer treated with curative intent,
   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 2 years are eligible).

Clinical Trial Information

Schema Lung Map

PROTOCOL: Lung Map

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

Step 0:

1. Patients with adequate archival tissue should be registered directly to Step 1, without registering to Step 0. Patients who need a fresh biopsy to obtain adequate tumor tissue must also submit whole blood for ctDNA testing. These patients must be registered to Step 0 to obtain a patient ID number for the submission.
2. Patients registered to Step 0 are not registered to the LUNGMAP protocol. To participate in LUNGMAP, patients must be registered to Step 1 after evaluation of patient eligibility, including tumor tissue adequacy.

Step 1:

1. Patients must have pathologically proven non-small cell lung cancer (all histologic types) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV or recurrent. All histologies, including mixed, are allowed.
2. Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment.
3. Screening at progression on prior treatment:
   To be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (Stages IIV) and must have progressed during or following their most recent line of therapy.
   1. 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 platinumbased chemotherapy must have occurred within one year from
      the last date that patient received that therapy. For patients treated with consolidation anti-PD-1 or anti-PD-L1 therapy for Stage III disease, disease progression on consolidation anti-PD1 or anti-PD-L1 therapy must have occurred within one year from
      the date of initiation of such therapy.
   2. 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 or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or
      Pembrolizumab).
4. Pre-Screening prior to progression on current treatment:
   To be eligible for pre-screening, current treatment must be for Stage IV or recurrent disease and patient must have received at least one dose of the current regimen. Patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or anti-PD-1/PDL1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab). Patients on first-line treatment are eligible upon receiving Cycle 1, Day 1 infusion. Note: Patients will not receive their sub-study assignment until they progress and the LUNGMAP Notice of Progression is submitted.
5. Patients must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥ 0.2 mm3 tumor volume.
   • The local interpreting pathologist must review the specimen.
   • The pathologist must sign the LUNGMAP Local Pathology Review Form confirming tissue adequacy prior to Step 1 registration.
6. Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling and PD-L1. If archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained. Patients who need the fresh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor block or FFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. If FFPE slides are to be submitted, at least 12
   unstained slides plus an H&E stained slide, or 13 unstained slides must be submitted. However, it is strongly recommended that 20 FFPE slides be submitted. Note: Previous next-generation DNA sequencing (NGS) will be repeated if done outside this study for sub-study assignment.
7. Patients must agree to have any leftover tissue (tissue that remains after biomarker testing) retained for the use of correlative studies outlined in the substudy treatment consents.
8. Patients with known EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, or BRAF V600E mutation are not eligible unless they have progressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testing is not required prior to Step 1 registration, as it is included in the Foundation One testing for screening/prescreening.
9. Patients must have Zubrod performance status 0-1.
10. Patients must be ≥ 18 years of age.

Clinical Trial Information

Schema EA5163

PROTOCOL: ECOG-EA5163

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must have histologically or cytologically confirmed stage IV non-squamous NSCLC (includes M1a, M1b, and M1c stage disease). Patients with T4NX disease (Stage IIIB and IIIC) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation.
2. Patients must have PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the
   testing could not be completed, the patients are not eligible.
3. Patients must have measurable or non-measureable disease.
4.  Patients must be ≥ 18 years of age.
5. Patients must have an ECOG Performance Status of 0 to 1.
6. Patients must NOT have received the following:
   1. Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for metastatic lung cancer are ineligible. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed between the last dose of the prior therapy and study registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 14 days has passed
      between completion of local therapy and study registration.
   2. Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
7. Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations that can be
   treated with oral tyrosine kinase inhibitors are excluded.
8. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
   1. Patients are eligible if off steroids for at least 14 days prior to protocol treatment.
   2. Anticonvulsants are allowed.
9. Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
10. Patients must not receive any other investigational agents during the course of therapy.

Clinical Trial Information

Schema E4512

PROTOCOL: ECOG-E4512

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Age ≥ 18 years.
2. Patients must have undergone complete surgical resection of their stage IB (≥ 4 cm), II, or non-squamous IIIA and have had negative margins. N3 disease is not allowed.
3. Baseline Chest CT with or without contrast must be performed within 6 months (180 days) prior to randomization to ensure no evidence of disease. If clinically indicated additional imaging studies must be performed to rule out metastatic disease.
4. ECOG performance status 0 or 1.
5. Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization.
6. Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in EML4-ALK fusion) as defined by a CLIA approved test including: (1) translocation or inversion events involving the ALK gene locus (e.g. resulting in EML4-ALK fusion) as determined by the Vysis Break Point FISH assay; (2) ALK protein expression by immunohistochemistry (IHC); or (3) ALK rearrangement identified by Next Generation (NextGen) sequencing.
7. Patients must be adequately recovered from surgery at the time of randomization. The minimum time requirement between date of surgery and randomization must be at least 4 weeks (28 days). The maximum time requirement between surgery and
   randomization must be:
   1. 3 months (90 Days) if no adjuvant chemotherapy was administered.
   2. 8 months (240 Days) if adjuvant chemotherapy was administered.
   3. 10 months (300 Days) if adjuvant chemotherapy and radiation therapy were administered.
8. Patients must have completed any prior adjuvant chemotherapy or radiation therapy 2 or more weeks (6 or more weeks for mitomycin
   and nitrosoureas) prior to randomization and be adequately recovered at the time of randomization.
   1. Patients taking low dose Methotrexate for non-malignant conditions and other cytotoxic agents for non-malignant conditions are allowed to continue treatment while on study.
   2. Neo-adjuvant chemotherapy or radiation therapy for the resected lung cancer is not permitted.
9. Patients must not have any history of locally advanced or metastatic cancer requiring systemic therapy within 5 years from randomization, with the exception of in-situ carcinomas and non-melanoma skin cancer. Patients must have no previous primary lung cancer diagnosed concurrently or within the past 2 years.
10. Patients may not be receiving any other investigational agents while on study.

Clinical Trial Information

Schema A151216

PROTOCOL: Alliance-A151216

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. For pre-surgical patients:
   1. Suspected diagnosis of resectable non-small cell lung cancer. Cancers with a histology of “adenosquamous” are considered a type of adenocarcinoma and thus a “non-squamous” histology. Patients with squamous cell carcinoma are eligible.
   2. Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size ≥4cm). Note: IB tumors <4cm are NOT eligible. Stage IB cancer based on pleural invasion is not eligible unless the tumor size is ≥4cm.
2. For post-surgical patients:
   1. Completely resected non-small cell lung cancer with negative margins (R0). Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy.
   2. Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size ≥4 cm). Note: IB tumors <4cm are NOT eligible. Stage IB cancer based on pleural invasion is not eligible unless the tumor size is ≥4cm. The 7th edition of AJCC staging will be utilized.
3. ECOG Performance Status 0-1.
4. Age ≥ 18 years.
5. No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer.
6. No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration. No secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration.
7. No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD1/PD-L1/CTLA-4.
8. Patients who have had local genotyping are eligible, regardless of the local result.
9. No patients with recurrence of lung cancer after prior resection.
10. Note: Post-surgical patients should proceed to registration immediately following pre-registration.
11. Tissue available for the required analyses (either clinical tissue block or slides and scrolls.
12. Completely resected NSCLC with negative margins (R0). Cancers with a histology of “adenosquamous” are considered a type of adenocarcinoma and thus a “nonsquamous” histology.
13. Pathologic stage IIIA, IIA or IIB, or large IB (defined as size ≥ 4cm). Note: IB tumors <4cm are NOT eligible. Stage IB cancer based on pleural invasion is not eligible unless the tumor size is ≥4cm.
14. Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy.