- Histologically confirmed metastatic squamous or non-squamous non-small cell lung
- Previously treated with at least one line of therapy including an immune checkpoint
blocker and no more than 2 prior lines in the metastatic setting.
- Documented PD-L1 expression of at least 1% by PharmDx 22C3 by a US FDA-approved PD-L1
assay from archival biopsy or fresh tumor tissue.
- At least one measurable lesion per RECIST 1.1 criteria.
- At least 18 years of age.
- ECOG performance status ≤ 1.
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 2.0 x IULN (except participants with Gilbert's syndrome who
must have total bilirubin < 3.0 mg/dL)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN without hepatic metastasis and ≤ 5.0 x IULN with
- Patients with brain or meningeal metastases are eligible provided they meet the
- No evidence of progression by neurologic symptoms or signs for at least 4 weeks
prior to first dose of study treatment
- Metastatic brain lesions that do not require immediate intervention
- No use of corticosteroids with dose above 10 mg prednisone (or equivalent)
- The effects of the study drugs on the developing human fetus are unknown. For this
reason, women of childbearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control, abstinence) prior to study
entry, for the duration of study participation, and for 100 days after completion of
study treatment. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately. Men
treated or enrolled on this protocol must also agree to use adequate contraception
prior to the study, for the duration of the study, and 100 days after completion of
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- A history of other malignancy with the exception of malignancies for which all
treatment was completed at least 2 years before registration and the patient has no
evidence of disease.
- Patients with EGFR mutation, ALK rearrangement, ROS1 fusion or RET fusion are excluded
from the study.
- Currently receiving any other investigational agents or having received any
investigational agents within 28 days or 5 half-lives of first dose of trial
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to zimberelimab, domvanalimab, etrumadenant, or other agents used
in the study. Known hypersensitivity to recombinant proteins or any excipient
contained in the trial formulations.
- Use of any live vaccines against infectious diseases within 28 days of first dose of
- Any gastrointestinal condition that would preclude the use of oral medications (e.g.
difficulty swallowing, nausea, vomiting, or malabsorption).
- History of trauma or major surgery within 28 days prior to the first dose of study
- Underlying medical conditions that in the investigator's opinion will make the
administration of study treatment hazardous, including but not limited to:
- Interstitial lung disease, including history of interstitial lung disease or
- Active viral, bacterial or fungal infection requiring parenteral treatment within
14 days of the initiation of study treatment
- Clinically significant cardiovascular disease
- A condition that may obscure the interpretation of toxicity determination or AEs
- History of prior solid organ transplantation
- Concurrent medical condition requiring the use of supra-physiologic doses of
corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive
medications (with the exception of absorbable topical corticosteroids).
- Positive test results for hepatitis B surface antigen, hepatitis C virus antibody,
hepatitis C qualitative RNA, or human immunodeficiency virus-1 antibody at screening.
- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
- Any active autoimmune disease or documented history of autoimmune disease or syndrome
that required systemic treatment in the past 2 years (i.e. with use of
disease-modifying agents, corticosteroids, or immunosuppressive drugs) except for
vitiligo or resolved childhood asthma/atopy.
- Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment
- Participants with asthma who require intermittent use of bronchodilators, inhaled
corticosteroids, or local corticosteroid injections will not be excluded from
this study. Participants on chronic systemic corticosteroids will be excluded.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.