Atezolizumab in Treating Participants with Stage IIIB-IV Non-small Cell Lung Cancer
- Patients with Stage IIIB/IV squamous or non-squamous NSCLC (American Joint Committee on Cancer 7th Edition Staging) who have had prior treatment with nivolumab or pembrolizumab will be enrolled in one of 3 parallel cohorts based on the following: * Cohort 1: patient with progressive disease on nivolumab or pembrolizumab as the BOR; progressive disease must be confirmed with a confirmatory scan ≥ 4 weeks after the 1st documented date of progression * Cohort 2: patients with stable disease as the BOR on a minimum of 12 weeks of therapy with nivolumab or pembrolizumab * Cohort 3: patients with partial or complete response as the BOR, followed by progressive disease, on nivolumab or pembrolizumab; a confirmatory scan at the time of disease progression must be performed ≥ 4 weeks after the 1st documented date of progression
- Patients must have resolution of toxic effects to grade 1 or less from prior therapy (except alopecia)
- Patients must sign informed consent form (ICF) and show ability and willingness to comply with the requirements of the study protocol
- Willingness to undergo a biopsy ≤ 6 weeks of the start of study treatment to obtain formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 15 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression • Archival tissue is acceptable if obtained within the protocol specified period and if there is no intervening therapy between the tumor biopsy and the initiation of atezolizumab; tumor tissue should be of good quality based on total and viable tumor content; fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable; for core-needle biopsy specimens, at least three cores should be submitted for evaluation * Patients who do not have tissue specimens meeting eligibility requirements will be required to undergo a biopsy during the screening period; acceptable samples include core-needle biopsies for deep tumor tissue (minimum of three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions * Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable
- Absolute neutrophil count (ANC) ≥ 1500 cells/uL within 14 days prior to the first study treatment (cycle 1, day 1)
- White blood cell (WBC) counts > 2500/uL within 14 days prior to the first study treatment (cycle 1, day 1)
- Lymphocyte count ≥ 300/uL within 14 days prior to the first study treatment (cycle 1, day 1)
- Platelet count ≥ 100,000/uL within 14 days prior to the first study treatment (cycle 1, day 1)
- Hemoglobin ≥ 9.0 g/dL within 14 days prior to the first study treatment (cycle 1, day 1)
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) within 14 days prior to the first study treatment (cycle 1, day 1) with the following exception: * Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN within 14 days prior to the first study treatment (cycle 1, day 1) with the following exception: * Patients with liver involvement: AST and/or ALT ≤ 5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN within 14 days prior to the first study treatment (cycle 1, day 1) with the following exception: ▪ Patients with documented liver involvement or bone metastases: alkaline phosphatase ≤ 5 x ULN
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation within 14 days prior to the first study treatment (cycle 1, day 1)
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for patients with solid malignancies
- 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 5 months after the last dose of atezolizumab
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; patients with an ECOG performance status of 2 will be allowed at the discretion of the treating investigator in agreement with the sponsor-investigator
- International normalized ratio (INR) and activated partial thromboplastin time (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
- 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)
- Adverse events (AEs) from prior anticancer therapy that have not resolved to grade ≤ 1 except for alopecia
- History of grade 4 immune-related adverse events requiring treatment with prednisone or history of grade 3 immune-related adverse events requiring prednisone > 10 mg/kg for > 12 weeks
- Bisphosphonate therapy for symptomatic hypercalcemia * Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
- Patients with acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
- Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases * Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met: ** Evaluable or measurable disease outside the CNS ** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) ** No history of intracranial hemorrhage or spinal cord hemorrhage ** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted ** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1 * Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following: ** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study ** Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids
- Patients who are pregnant, are lactation, or breastfeeding
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Inability to comply with study and follow-up procedures
- 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, Sjogren’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) ** Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%) ** No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
- 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 * History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- 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
- 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 HCV ribonucleic acid (RNA)
- Active tuberculosis
- 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
- Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
- Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1 * Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
- Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
- Administration of a live, attenuated vaccine within 4 weeks before enrollment or anticipation that such a live attenuated vaccine will be required during the study or for 5 months after the last dose of atezolizumab * 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 enrollment, at any time during the study, or for 5 months after the last dose of atezolizumab
- Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, 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., chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score ≤ 6, and prostate-specific antigen [PSA] ≤ 10 mg/mL, etc.)
- 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)
- Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-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
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
I. To estimate the best overall response (BOR) of atezolizumab in patients previously treated with PD-1 directed therapy, in each of three parallel cohorts defined by BOR to PD-1 directed therapy.
I. To estimate the duration of response (DOR) of atezolizumab in patients previously treated with anti-PD-1 therapy, based on the BOR to PD-1 directed therapy.
II. To estimate the progression-free survival (PFS) of atezolizumab in patients previously treated with anti-PD-1 therapy, based on the BOR to PD-1 directed therapy.
III. To estimate the overall survival (OS) of atezolizumab in patients previously treated with anti-PD-1 therapy, based on the BOR to PD-1 directed therapy.
IV. To estimate the safety of atezolizumab in patients previously treated with anti-PD-1 therapy, as determined by grade ≥ 3 treatment related adverse events.
I. To understand mechanisms of immune escape and assess biomarkers of response, including but not limited to PD-L1 expression.
Participants receive atezolizumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days, and for up to 12 months thereafter.
Trial Phase Phase II
Trial Type Treatment
University of Pittsburgh Cancer Institute (UPCI)
Liza C. Villaruz
- Primary ID 16-153
- Secondary IDs NCI-2018-00772
- Clinicaltrials.gov ID NCT03014648