Overview

Atezolizumab for Idiopathic Pulmonary Fibrosis

Status:
Not yet recruiting
Trial end date:
2026-04-30
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to determine the safety and preliminary efficacy of atezolizumab, an immune checkpoint inhibitor approved for the treatment of various cancers, in patients with idiopathic pulmonary fibrosis (IPF).
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Cedars-Sinai Medical Center
Collaborator:
Genentech, Inc.
Treatments:
Atezolizumab
Criteria
Inclusion Criteria:

- Males or females ≥50 years of age

- Confident diagnosis of IPF per 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline on
Diagnosis of IPF1

- Subjects must have a high-resolution computed tomography (HRCT) completed in the
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 surgical lung
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 to
consent 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 positive total
HBcAB test followed by a negative hepatitis B virus (HBV) DNA test at screening. The
HBV DNA test will be performed only for patients who have a positive total HBcAb test.

- Negative hepatitis C antibody

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods, and agreement to refrain from
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 as defined
by > 10% decline in FVC or new requirement for supplemental oxygen

- Evidence of secondary etiologies of ILD (signs/symptoms of connective tissue disease,
including ANA titer > 1:80, history of exposures related to hypersensitivity
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 to
either screening or dosing

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

- Participation in a clinical study involving administration of other investigational
drugs in the 30 days prior to screening

- Any condition that in the opinion of the investigators would confound the ability to
interpret 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 to
endothelium 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 or
immunosuppressive medications, cytokine modulating therapies, and oral anticoagulants
within 4 weeks of the screening visit. Note: oral anticoagulants taken for alternative
diagnoses are acceptable and should not be discontinued for the 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 Visit or
short-acting bronchodilator within 8 hours of the Screening Visit

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

- Active or history of recurrent bacterial, viral, fungal, mycobacterial or other
infections (including, but not limited to, atypical mycobacterial disease and herpes
zoster), or any major episode of infection requiring hospitalization or treatment with
intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any 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 of
successful completion of a standard course of treatment for latent TB

- Diagnosis of any clinically significant autoimmune disease, with the exclusion of
vitiligo and diabetes mellitus.

- Pregnancy or lactation

- History of leptomeningeal disease

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently) Patients with indwelling
catheters (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 or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
months prior to initiation of study treatment, unstable arrhythmia, or unstable angina

- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation
of study treatment, or anticipation of need for a major surgical procedure during the
study

- History of malignancy, with the exception of malignancies with a negligible risk of
metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma
in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, 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 clinical
laboratory finding that contraindicates the use of an investigational drug, may affect
the interpretation of the results, or may render the patient at high risk from
treatment complications

- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment, or anticipation of need for such a vaccine during atezolizumab treatment 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 humanized antibodies
or fusion proteins

- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation

- Women of childbearing potential must have a negative serum pregnancy test result
within 14 days prior to initiation of study treatment.

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