Inclusion Criteria:
1. Male /female participants who are at least 20 years of age on the day of signing
informed consent with histologically confirmed diagnosis of
2. Histologically confirmed non-small cell carcinoma
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the date of
allocation/randomization.
4. Received one or two cytotoxic chemotherapy for advanced NSCLC including at least one
platinum-doublet
5. Has received prior therapy with an anti-PD-1, anti-PD-L1 agents (monotherapy) and
progression to last PD-1/PD-L1 inhibitors. The last PD-1/PD-L1 inhibitor should be
administered 6 weeks before the study enrollment, and no other systemic therapy should
be done between the interval.
6. At least one measurable lesion Have measurable disease based on RECIST 1.1. Lesions
situated in a previously irradiated area are considered measurable if progression has
been demonstrated in such lesions.
7. Available data for PD-L1 IHC results (any of one tested by 22C3, SP263, or SP142)
irrespective of expression level.
8. EGFR and ALK wild type
Exclusion Criteria:
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
[randomization/allocation] (see Appendix 3). If the urine test is positive or cannot
be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior systemic anti-cancer therapy including investigational agents
within 3 weeks [could consider shorter interval for kinase inhibitors or other short
half-life drugs] prior to [randomization /allocation].
Note: Participants must have recovered from all AEs due to previous therapies to
≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
Note: If participant received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting study
treatment.
3. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
4. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
5. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 3 weeks prior to the first dose of
study treatment.
Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, well differentiated thyroid carcinoma, or
carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone
potentially curative therapy are not excluded.
8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment. Patients with oligo (≤5) brain metastasis with size
less than 1cm can be enrolled without prior radiotherapy, if the tumors are regarded
as asymptomatic and stable, based on follow-up brain MRIs checked intervals of at
least 3 months. However, all patients with previously non-irradiated brain metastases
should have brain MRI checked within 4 weeks before starting administration of study
drugs.
9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any PD-1/PD-L1
inhibitors.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
11. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
12. Has an active infection requiring systemic therapy.
13. Has a known history of Human Immunodeficiency Virus (HIV)
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
15. Has a known history of active TB (Bacillus Tuberculosis).
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
