Atezolizumab for Idiopathic Pulmonary Fibrosis

Inclusion Criteria:

• Males or females ≥50 years of age

• Confident diagnosis of IPF per 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline onDiagnosis of IPF1

• Subjects must have a high-resolution computed tomography (HRCT) completed inthe 6 months prior to informed consent

• Subjects must have HRCT pattern of definite or probable UIP

• Subjects without HRCT pattern of definite or probable UIP must have surgicallung biopsy showing histopathology consistent with UIP

• Extent of fibrotic changes must be greater than the extent of emphysema on HRCT

• Review of all available IPF treatment options with the potential subject prior toconsent for participation in the study

• Negative hepatitis B surface antigen (HBsAg) test at screening

• Negative total hepatitis B core antibody (HBcAb) test at screening, or positivetotal HBcAB test followed by a negative hepatitis B virus (HBV) DNA test atscreening. The HBV DNA test will be performed only for patients who have a positivetotal HBcAb test.

• Negative hepatitis C antibody

• For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive methods, and agreement to refrainfrom donating eggs, as defined below:

Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Women must refrain from donating eggs during this same period.

A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.

Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:

With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after the final dose of atezolizumab to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.

Exclusion Criteria:

• FVC <50% of predicted, DLCO < 30% of predicted, FEV1/FVC ratio <0.7

• Significant clinical worsening of IPF between screening and baseline visits asdefined by > 10% decline in FVC or new requirement for supplemental oxygen

• Evidence of secondary etiologies of ILD (signs/symptoms of connective tissuedisease, including ANA titer > 1:80, history of exposures related tohypersensitivity pneumonitis, history of drug-related pulmonary toxicity,occupational exposures)

• Evidence of comorbid pulmonary pathology including but not limited to asthma,tuberculosis, sarcoidosis, chronic infections

• Any acute illness or febrile event that has not resolved at least 14 days prior toeither screening or dosing

• Use of tobacco-containing products within the last 3 months and/or unwillingness toabstain from use for the duration of the study

• Participation in a clinical study involving administration of other investigationaldrugs in the 30 days prior to screening

• Any condition that in the opinion of the investigators would confound the ability tointerpret data from the study

• QTc > 470 msec

• Any comorbid condition that is likely to result in death within the next year

• Inability to obtain reproducible, high-quality pulmonary function tests

• Likelihood of lung transplantation in the first 24 weeks of the study

• Use of other IPF-directed therapies beside SOC including but not limited toendothelium receptor antagonists, interferon gamma-1b, N-acetylcysteine

• Initiation of pirfenidone or nintedanib less than 90 days prior to screening

• Current therapy or treatment within 60 days prior to screening of any cytotoxic orimmunosuppressive medications, cytokine modulating therapies, and oralanticoagulants within 4 weeks of the screening visit. Note: oral anticoagulantstaken for alternative diagnoses are acceptable and should not be discontinued forthe sole purpose of study participation.

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies,including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

• Use of an inhaled long-acting bronchodilator within 24 hours of the Screening Visitor short-acting bronchodilator within 8 hours of the Screening Visit

• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 6 months ofthe Screening Visit and/or recurrent DVT or recurrent PE

• Active or history of recurrent bacterial, viral, fungal, mycobacterial or otherinfections (including, but not limited to, atypical mycobacterial disease and herpeszoster), or any major episode of infection requiring hospitalization or treatmentwith intravenous or oral antibiotics within 4 weeks of the Screening Visit and atany time during the Screening Phase, up through the first dose of study drug

• History of latent or active TB, unless there is medical record documentation ofsuccessful completion of a standard course of treatment for latent TB

• Diagnosis of any clinically significant autoimmune disease, with the exclusion ofvitiligo and diabetes mellitus.

• Pregnancy or lactation

• History of leptomeningeal disease

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrentdrainage procedures (once monthly or more frequently) Patients with indwellingcatheters (e.g., PleurX) are allowed.

• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)

• Significant cardiovascular disease (such as New York Heart Association Class II orgreater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstableangina

• Major surgical procedure, other than for diagnosis, within 4 weeks prior toinitiation of study treatment, or anticipation of need for a major surgicalprocedure during the study

• History of malignancy, with the exception of malignancies with a negligible risk ofmetastasis or death (e.g., 5-year OS rate > 90%), such as adequately treatedcarcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostatecancer, ductal carcinoma in situ, or Stage I uterine cancer

• Prior allogeneic stem cell or solid organ transplantation

• Any other disease, metabolic dysfunction, physical examination finding, or clinicallaboratory finding that contraindicates the use of an investigational drug, mayaffect the interpretation of the results, or may render the patient at high riskfrom treatment complications

• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation ofstudy treatment, or anticipation of need for such a vaccine during atezolizumabtreatment or within 5 months after the final dose of atezolizumab

• Current treatment with anti-viral therapy for HBV

• History of severe allergic anaphylactic reactions to chimeric or humanizedantibodies or fusion proteins

• Known hypersensitivity to Chinese hamster ovary cell products or to any component ofthe atezolizumab formulation

• Women of childbearing potential must have a negative serum pregnancy test resultwithin 14 days prior to initiation of study treatment.

• Patients at increased risk of adverse outcomes given the known safety profile foratezolizumab and SOC medications (hepatitis, colitis, endocrinopathies,nephritis/renal dysfunction, exfoliative dermatitis)