Clinical trial NCT02525757 (phase 2, status: active, not recruiting)
Conditions: lung cancer, non-small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2, C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: mpdl3280a, carboplatin, paclitaxel
SMILES: N[C@@H](CCCNC(N)=N)C(O)=O, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
Eligibility criteria:

        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