- Patient must be capable, willing, and able to provide written, informed consent
- Age ≥ 18 years old
- Histologically-confirmed stage IIIb or IV NSCLC by the enrolling institution
a. Patients who are highly suspected to have stage IIIb or IV NSCLC and who are
planned for a standard-of-care diagnostic biopsy/resection may also be enrolled.
Patients who are confirmed to have stage IIIb or IV NSCLC will be eligible to continue
with screening procedures. Those who are found after surgery/biopsy to not have stage
IIIb or IV NSCLC will not be eligible continue with screening procedures and may not
receive study therapy.
- Previously treated with no more than one line of prior systemic therapy for stage IIIb
or IV lung cancer.
1. For patients who have previously treated one line of prior systemic therapy for
stage IIIb or IV lung cancer, they must have exhibited evidence of disease
progression clinically and/or radiographically on or after that treatment.
2. Patients who previously received neoadjuvant, concurrent, or adjuvant
chemotherapy for localized NSCLC and then recurred within 6 months of completing
chemotherapy will be considered as having received one line of prior therapy.
Patients who relapse > 6 months after completing chemotherapy as part of
neoadjuvant/concurrent/adjuvant therapy for localized disease, and thereafter
receive additional one line of chemotherapy at the time of metastatic disease
will be eligible.
3. Maintenance therapy does not count as a separate line of therapy
- Measurable by RECIST v1.1 (those undergoing pre-treatment resection must have imaging
assessment after resection to determine measurability)
a. Previously irradiated sites of tumor may be considered measurable if there is
radiographic progression at that site subsequent to the time of completing radiation.
- Have a safely biopsiable tumor lesion and be willing to undergo a pre-treatment and
ontreatment core biopsy a. Pretreatment tissue should be collected via core biopsy,
ideally of a non-target lesion. b. Patients may not have intervening systemic
anti-cancer therapy between the time of pre-treatment biopsy/resection and initiating
- ECOG performance status of 0-1.
- Adequate hematologic, renal, and/or hepatic function (following criteria must be met
within 28 days of C1D1):
1. ANC ≥ 1,500/mm3 (≥ 1. 5 × 10^9/L)
2. Hemoglobin ≥ 9.0 g/dL
3. Platelet count ≥ 100,000/ul (≥ 100,000 per mm3)
4. Serum creatinine ≤ 1.5 x ULN OR, for subjects with creatinine levels >1.5 x ULN,
an estimated creatinine clearance of ≥ 40 mL/min calculated using the Cockcroft
and Gault formula ((140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by
0.85 if female)
5. Total bilirubin ≤ 1.5 x ULN OR, for subjected with total bilirubin levels >1.5 x
ULN, a direct bilirubin ≤ ULN
6. AST and ALT ≤ 3 x UNL (unless elevated transaminases are felt to be directly
related to metastatic disease involving the liver, in which case AST and ALT must
be ≤ 5x ULN)
- Women of childbearing potential (WOCBP) † must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days
† A woman of childbearing potential is a sexually mature female who: has not undergone
a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for
at least 24 consecutive months (i.e. has had menses at any time in the preceding 24
- Effective contraception:
1. Women of childbearing potential must agree to practice 2 effective methods of
contraception from the time of signing the informed consent form through 120 days
after the last dose of study therapy, or agree to completely abstain from
2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must
agree to 1 of the following: practice effective barrier contraception during the
entire study treatment period and through 120 days after the last dose of study
therapy, or agree to completely abstain from heterosexual intercourse.
- Willing to comply with clinical trial instructions and requirements, including
- Presence of targetable EGFR mutations or ALK re-arrangements.
a. All patients with adenocarcinoma histology must be tested for EGFR and ALK status,
unless a KRAS mutation is detected in which case EGFR/ALK testing is not required.
- History of allergy to study drug components or history of severe hypersensitivity
reaction of any monoclonal antibody.
- History of (non-infectious) pneumonitis that required steroids, or current
- Prior treatment with immune checkpoint inhibitor, including (but not limited to) those
targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40.
- Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy, with
the following exception:
a. Any prior investigational anti-cancer therapy and/or monoclonal antibody is not
permitted within 4 weeks of C1D1.
- Ongoing adverse event from previously administered systemic anti-cancer therapy unless
has recovered to ≤ grade 1 or at baseline prior to C1D1.
a. Subjects with any grade alopecia or ≤ Grade 2 neuropathy are an exception to this
criterion and may qualify for the study.
- Patients who have not previously been treated with platinum-based based doublet
chemotherapy and who, in the judgment of the investigator, have rapidly progressive
disease such that serious complications may arise from disease progression within the
next 12 weeks will be excluded.
- Non-CNS radiotherapy within 1 week prior to C1D1 of study therapy
- Active infection requiring systemic therapy
- Known history of previous clinical diagnosis of tuberculosis.
- Prior or current systemic immunosuppressive therapy (> 10 mg/day prednisone
equivalents) within 7 days prior to C1D1 of study therapy. Inhaled, ocular,
intra-articular, intranasal, and topical corticosteroids are permitted in absence of
active autoimmune disease.
a. Adrenal replacement doses are permitted in the absence of active autoimmune
- Has diagnosis of immunodeficiency
- History of allogeneic organ transplant.
- Patients with known or suspected history of autoimmune disease.
a. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone
replacement, resolved childhood asthma/atopy, patients with asthma requiring
intermittent bronchodilator therapy, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment, or conditions not expected to recur in the
absence of an external trigger are permitted to enroll. i. Replacement therapy (e.g.,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Other active malignancy that is progressing, requires concurrent intervention, and/or
could be mistaken for the malignancy under study during disease assessments.
- Patients with previous malignancies (except non-melanoma skin cancers, and the
following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or
breast) are excluded unless definitive therapy has been completed at least 1 year
prior to study entry and the patient is now without evidence of disease from that
malignancy and no additional therapy is required or anticipated to be required during
the study period.
- Known untreated brain or leptomeningeal metastasis.
a. Patients with brain metastases are eligible if metastases have been adequately
treated and neurologically returned to baseline (except for residual signs or symptoms
related to the CNS treatment) for at least two weeks prior to C1D1 and meet
requirements related to steroids noted in above Exclusions Criteria 6.2.10.
- History of stroke or transient ischemic attack within the previous 6 months.
- Any of the following cardiac abnormalities:
1. Unstable angina pectoris
2. Congestive heart failure ≥ NYHA Class 3
3. QTc ≥470 milliseconds calculated using Frediricia's Correction
4. Current or history of pericardial effusion causing hemodynamic compromise
- History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis
which required steroid treatment, or any evidence of clinically active interstitial
- Any positive test for HIV 1/2 antibodies and/or RNA.
- Any positive test for hepatitis B virus(HBV) using HBV surface antigen (HBV sAG) test
or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
antibody test indicating acute or chronic infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
- Has received a live vaccine within 30 days of planned start of study therapy. a.
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.