| Eligibility |
Inclusion Criteria:
- 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
best overall response. 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 best overall response on a minimum
of 12 weeks of therapy with nivolumab or pembrolizumab.
- Cohort 3: Patients with partial or complete response as the best overall response
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.
- Both men and women of all races and ethnic groups are eligible for this trial
- Patients must have resolution of toxic effects to Grade 1 or less from prior therapy
(except alopecia).
- Patients must sign Informed Consent Form and show ability and willingness to comply
with the requirements of the study protocol.
- 18 years of age or older
- Willingness to undergo a biopsy = 6 weeks of the start of study treatment to obtain
formalin-fixed paraffin-embedded 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.
- 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):
- ANC equal to/greater than 1500 cells/µL
- WBC counts greater than 2500/µL
- Lymphocyte count equal to/greater than 300µ/L
- Platelet count equal to/greater than 100,000/µL
- Hemoglobin equal to/greater than 9.0 g/dL
- Total bilirubin equal to/less than 1.5 x ULN with the following exception:
- Patients with known Gilbert disease who have serum bilirubin level equal
to/less than 3 x ULN may be enrolled.
- AST and ALT equal to/less than 3.0 x ULN with the following exception:
- Patients with liver involvement: AST and/or ALT equal to/less than 5 x ULN
- Alkaline phosphatase equal to/less than 2.5 x ULN with the following exception:
- Patients with documented liver involvement or bone metastases: alkaline
phosphatase equal to/less than 5 x ULN
- Serum creatinine equal to/less than 1.5 x ULN or creatinine clearance equal to/greater
than 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate
estimation.
- Measurable disease per 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 [less than 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 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.
- INR and aPTT equal to/less than 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:
- 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 greater than 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).
- Hormonal therapy for prostate cancer or breast cancer provided criteria in 3.2.21
are met.
- Palliative radiotherapy (e.g., treatment of known bony metastases) allowed,
provided it does not interfere with the assessment of tumor target lesions
(e.g. the lesion being irradiated is not the only site of disease, because
that would render the patient not evaluable for response by tumor
assessments according to RECIST v1.1).
- Adverse events from prior anticancer therapy that have not resolved to Grade equal
to/less than1 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.
- No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle
1, Day 1.
- Screening CNS radiographic study equal to/greater than 4 weeks from completion of
radiotherapy and equal to/greater than 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, 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).
- 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 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 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 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 equal to/less
than 6, and prostate-specific antigen equal to/less than10 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.
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