MPDL3280A With Chemoradiation for Lung Cancer
MPDL3280A With Chemoradiation for Lung Cancer
The goal of this clinical research study is to learn about the safety of adding MDPL3280A to
 standard chemotherapy (a combination of carboplatin and paclitaxel) and radiation in patients
 with lung cancer.

 You are being asked to take part in this study because you have non-small cell lung cancer
 (NSCLC) that is unresectable (cannot be removed by surgery) and has not spread.

 This is an investigational study. MPDL3280A is not FDA approved or commercially available. It
 is currently being used for research purposes only. Paclitaxel, carboplatin, and the
 radiation therapy are all FDA approved for the treatment of lung cancer. The use of these
 drugs in combination is considered investigational.

 Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.
Study Groups and Study Drug Administration:

 Each study cycle is 21 days.

 If you are found to be eligible to take part in this study, depending on when you join the
 study, you will be assigned to 1 of 2 study groups. Up to 10 participants will be assigned to
 Group 1 and up to 30 will be assigned to Group 2.

 Participants in Groups 1 and 2 will receive standard chemotherapy 1 time each week and
 radiation therapy 5 days per week as described below Every cycle you will also receive
 MPDL3280A by vein over about 1 hour.

 If you are in Group 1, you will receive standard chemotherapy and radiation for 6-7 weeks,
 followed by around a 3-8 week "rest period" when you will receive no chemotherapy or
 radiation.

 If you are in Group 2, you will receive MPDL3280A, standard chemotherapy, and radiation
 therapy for 6-7 weeks. This will be followed by a rest period of 3-4 weeks, during which time
 you will receive 1 dose of MPDL3280A but no chemotherapy or radiation.

 After the rest period, Groups 1 and 2 will both receive MPDL3280A in addition to chemotherapy
 for 2 cycles (called the consolidation period). After completing the consolidation period,
 you will continue to receive MPDL3280A alone for up to 1 year (called the maintenance
 period).

 During your first dose of MPDL3280A, your vital signs (blood pressure, pulse, temperature,
 and breathing rate) will be measured 60 minutes before the dose, every 15 minutes during the
 dose, and 30 minutes after the dose to check for any bad reaction to the study drug. You may
 be given standard drugs to help with side effects.

 If you need to stop receiving chemotherapy due to side effects, you will also stop receiving
 MPDL3280A. If you stop receiving chemotherapy for any other reason, you may continue
 receiving MPDL3280A.

 Study Visits:

 Once a week during Weeks 1-7:

 -  You will have a physical exam.

 -  Blood (up to 2 teaspoons) will be drawn for routine tests and to check your liver and
 kidney function.

 Between Weeks 8-16 you will have a rest period. The rest period could range from 3-8 weeks,
 after which time you will return for the consolidation period.

 One (1) time during consolidation period, which starts after the rest period, during Weeks
 1-3 and Weeks 4-6 of the consolidation period:

 -  You will have a physical exam.

 -  Blood (up to 2 teaspoons) will be drawn for routine tests and to check your liver and
 kidney function.

 -  You will have either a CT scan or an FDG-PET/CT scan to check the status of the disease.

 After you complete the consolidation period, you will enter the maintenance period. During
 every cycle of the maintenance period, blood (about 2 teaspoons) will be drawn for routine
 tests.

 Every 2 cycles during the maintenance period, for up to 1 year:

 -  You will have a physical exam.

 -  You will have either a CT scan or an FDG-PET/CT scan to check the status of the disease.

 If the disease appears to come back at any time during the study:

 -  You will have a physical exam.

 -  You will have a CT scan or MRI of the brain to check the status of the disease.

 -  You will have either a CT scan or an FDG-PET/CT of your chest and abdomen to check the
 status of the disease.

 -  You will have a biopsy of any suspicious areas found on the scans to check the status of
 the disease.

 -  Your doctor may choose to continue the study drug and repeat the scans in 6-8 weeks to
 check the status of the disease.

 -  If your doctor feels that the study drug is no longer effective from the information
 obtained from the repeat scans, you will be taken off the study drug. You will continue
 to be followed up by a schedule determined by your doctor.

 -  Your doctor may offer alternative treatments if your doctor feels it is in your best
 interest.

 Length of Treatment:

 You may receive the study drug for up to 1 year after starting the consolidation period, as
 long as the doctor thinks it is in your best interest. You will no longer be able to receive
 study drug if the disease gets worse, if intolerable side effects occur, or if you are unable
 to follow study directions.

 If you are taken off study during the consolidation or maintenance period due to intolerable
 side effects, you will be followed by the study staff as often the doctor thinks is needed
 until the side effects get better.

 Your active participation on the study will be over after the follow-up visits.

 Follow-up Visits:

 You will have follow-up visits every 2-4 months for up to 2 years after your last dose of
 study drug, unless you leave the study due to side effects or the disease having appeared to
 come back. After 2 years, you will have follow-up visits about every 4-6 months based on what
 your doctor thinks is best.

 At each follow-up visit, the following tests will be performed:

 -  You will have a physical exam.

 -  You will have either a CT scan or an FDG-PET/CT scan of your chest and abdomen to check
 the status of the disease.

 -  If your doctor thinks it is needed, blood (up to 2 teaspoons) will be drawn for routine
 tests and to check your liver and kidney function.

 If you cannot return to MD Anderson for these visits, you may be called by a member of the
 study staff every 3-6 months for 4 years after the last dose of study drug. Each call should
 last about 10 minutes. The study staff may ask that any tests or scans done by your home
 doctor be sent to MD Anderson to check the status of the disease.
Inclusion Criteria:

 1. Ability and willingness to provide informed consent

 2. Ability and willingness to comply with the requirements of the study protocol

 3. Age >/= 18 years.

 4. Representative tumor specimens in paraffin blocks (preferred) or at least 10 unstained
 slides, with an associated pathology report, requested at any time prior to study
 entry. Only tissue from core needle, punch, or excisional biopsy sample collection
 will be accepted. Fine-needle aspiration, brushing, and lavage samples are not
 acceptable. For all biopsy types, submitted blocks should have sufficient tissue to
 generate at least 10 sections, and tissue for which the pathology report specifies
 that the overall tumor content is low (e.g., "sparse" or "scant") is not acceptable.

 5. Cont'd from #4: If archival tissue is either insufficient or unavailable, the patient
 will need to consent to and undergo a pre treatment core or excisional biopsy sample
 collection of the tumor. Fine needle aspiration, brushing, and lavage samples are not
 acceptable. The immediate unavailability of tissue blocks or unstained slides aside
 from the slides needed for diagnostic confirmation of lung cancer does not exclude
 patients from this trial. If the patient chooses to not undergo a repeat biopsy aside
 from biopsy for diagnostic purposes, the patient will still be eligible to enroll on
 2014-0722. However, availability of core or excisional biopsy samples must be
 ascertained prior to enrollment.

 6. Patients must have histologically confirmed, untreated non-small cell lung cancer that
 are considered non-metastatic, unresectable for which chemoradiation is the definitive
 therapy.

 7. Patients will have the option to enroll on blood collection protocol, LAB09-0983, for
 serial collections of blood before, during intervals of treatment, and at follow up
 visits. Enrolling on the LAB09-0983 protocol is not required to enroll on the
 2014-0722 study.

 8. Adequate hematologic and end organ function, defined by the following laboratory
 results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
 Absolute neutrophil count (ANC) >/= 1500 cells/uL *White Blood Cells (WBC) counts >
 2500/uL *Lymphocyte count >/= 500/uL *Platelet count >/= 100,000/uL; for patients with
 hematologic malignancies, platelet count >/= 75,000/uL *Hemoglobin >/= 9.0 g/dL *Total
 bilirubin </= 1.5 x Upper Limit of Normal (ULN) with the following exception: Patients
 with known Gilbert disease who have serum bilirubin level </= 3 x ULN may be enrolled.
 *Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) </= 3.0 x ULN

 9. Cont'd from #8: Serum creatinine </= 1.5 x ULN or creatinine clearance >/= 50 mL/min
 on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age)
 x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL)

 10. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

 11. For female patients of childbearing potential and male patients with partners of
 childbearing potential, agreement (by patient and/or partner) to use highly effective
 form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year]
 when used consistently and correctly) and to continue its use for 12 months after the
 last dose of MPDL3280A, and for male patients continued use of contraception must be
 for a minimum of 3 months post-treatment.

 12. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 as long as
 patients are eligible to receive chemotherapy along with concurrent radiotherapy

 13. International Normalized (INR) and aPTT </= 1.5 x ULN * This applies only to patients
 who do not receive therapeutic anticoagulation; patients receiving therapeutic
 anticoagulation (such as low-molecular weight heparin or warfarin) should be on a
 stable dose.

 Exclusion Criteria:

 1. Patients with any distant metastasis (liver, lung, bone, brain).

 2. Any approved anticancer therapy, including chemotherapy, hormonal therapy, or
 radiotherapy, within 3 weeks prior to initiation of study treatment; however, the
 following are allowed: *Hormone-replacement therapy or oral contraceptives *Herbal
 therapy > 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer
 therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)

 3. Known clinically significant liver disease, including active viral, alcoholic, or
 other hepatitis, cirrhosis, fatty liver, and inherited liver disease

 4. Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia,
 chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory
 myeloma

 5. Pregnancy, lactation, or breastfeeding

 6. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
 human antibodies

 7. Inability to comply with study and follow-up procedures

 8. History or risk of autoimmune disease, including but not limited to systemic lupus
 erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
 associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
 syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
 thyroid disease, vasculitis, or glomerulonephritis *Patients with a history of
 autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be
 eligible. *Patients with controlled Type 1 diabetes mellitus on a stable insulin
 regimen may be eligible. *Patients with eczema, psoriasis, lichen simplex chronicus of
 vitiligo with dermatologic manifestations only (e.g., patients with psoriatic
 arthritis would be excluded) are permitted provided that they meet the following
 conditions: *Patients with psoriasis must have a baseline ophthalmologic exam to rule
 out ocular manifestations *Rash must cover less than 10% of body surface area (BSA)

 9. Cont'd from #9: *Disease is well controlled at baseline and only requiring low potency
 topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
 fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) *No acute
 exacerbations of underlying condition within the last 12 months (not requiring PUVA
 [psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents,
 oral calcineurin inhibitors, high potency or oral steroids)

 10. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
 organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
 pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
 tomography (CT) scan

 11. Any other diseases, metabolic dysfunction, physical examination finding, or clinical
 laboratory finding giving reasonable suspicion of a disease or condition that
 contraindicates the use of an investigational drug or that may affect the
 interpretation of the results or render the patient at high risk from treatment
 complications

 12. History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic
 or acute) or hepatitis C infection *Patients with past or resolved hepatitis B
 infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a
 positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
 *Patients positive for hepatitis C virus (HCV) antibody are eligible only if
 polymerase chain reaction (PCR) is negative for hepatitis C virus ribonucleic acid
 (HCV RNA).

 13. Active tuberculosis

 14. Severe infections within 4 weeks prior to Cycle 1, Day 1 including but not limited to
 hospitalization for complications of infection, bacteremia, or severe pneumonia

 15. Signs or symptoms of severe infection (sepsis) within 2 weeks prior to treatment
 start.

 16. Major surgical procedure within 28 days prior to treatment start or anticipation of
 need for a major surgical procedure during the course of the study (EBUS and
 mediastinoscopy and VATS are not considered major surgical procedures).

 17. Administration of a live, attenuated vaccine within 4 weeks before treatment start or
 anticipation that such a live attenuated vaccine will be required during the study
 *Influenza vaccination should be given during influenza season only (approximately
 October to March). Patients must not receive live, attenuated influenza vaccine (e.g.,
 FluMist) within 4 weeks prior to treatment start or at any time during the study.

 18. Malignancies within 3 years prior to treatment start, with the exception of those with
 a negligible risk of metastasis or death and with expected curative outcome (such as
 adequately treated carcinoma in situ of the cervix, basal or squamous cell skin
 cancer, localized prostate cancer treated surgically with curative intent, or ductal
 carcinoma in situ treated surgically with curative intent) or undergoing active
 surveillance per standard-of-care management (e.g., CLL Rai Stage 0, prostate cancer
 with Gleason score </= 6, and PSA </= 10 mg/mL, etc.)

 19. FOLLOWING ARE Medication-Related Exclusion Criteria: *Treatment with systemic
 immunostimulatory agents (including but not limited to IFN-a, IL-2) within 6 weeks or
 five half-lives of the drug (whichever is shorter) prior to the start of
 chemoradiation.Treatment with investigational agent within 4 weeks prior to Cycle 1,
 Day 1 (or within five half lives of the investigational product, whichever is longer)

 20. Treatment with systemic immunosuppressive medications (including but not limited to
 prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
 necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1 *Patients who
 have received acute, low dose, systemic immunosuppressant medications (e.g., a
 one-time dose of dexamethasone for nausea) may be enrolled. *The use of inhaled
 corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with
 orthostatic hypotension or adrenocortical insufficiency is allowed.

 21. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
 chimeric or humanized antibodies or fusion proteins

 22. Patients with prior allogeneic bone marrow transplantation or prior solid organ
 transplantation