This study is a phase II, single-arm, open label study. All participating patients must sign
on the written informed consent form, and a separate form of consent will be used for the use
of tissue for the biomarker research.
This clinical study is targeted for the patients who harbor KRAS/NRAS mutation or no
actionable genetic abnormalities detected using NGS platform and all patients will be treated
with PDR001. The treatment period begins on Day 1 of Cycle 1 and 1 cycle consists of 21 days.
Patients will be continued to receive study drug until the end of study unless the patients
in disease progression, unacceptable toxicity, withdrawn consent, or by the investigator's
judgment.
The progression of the disease in most patients is defined radiographically and determined
according to RECIST criteria ver. 1.1. If there are patients those who need to be provided
investigational drug beyond predefined end of treatment, additional extended providing of
PDR001 needs the mutual agreement of the investigators and Novartis followed by amendment of
study protocol and contract.
At the investigator's discretion, patients who have the initial RECIST PD may continue
PDR001. At any time, if assessed by the investigator that the patient is no longer benefiting
from PDR001, or the patient experiences a second PD by RECIST, then the patient shall come
off study medication.
Inclusion Criteria:
- Subjects with histologically or cytologically confirmed, stage IV or recurrent NSCLC
that carries a KRAS/NRAS mutation or no actionable mutation, which are identified by
NGS.
- Squamous cell carcinoma and non-squamous cell carcinoma will be enrolled with 1:1
ratio for efficacy analysis according to histology
- Subjects who did not treated with prior anti-PD-1 antibody nor anti-PD-L1 antibodies
- ECOG performance status of 0 to 2
- Male or female; ≥ 18 years of age
- Patients those who showed disease progression after one or two prior
platinum-containing regimen
- Patients who have received prior platinum-containing adjuvant, neoadjuvant, or
definitive chemoradiation for locally advanced disease are eligible, provided that
progression has occurred ≥ 12 months from last therapy.
- Subjects with at least one measurable lesion (using RECIST 1.1 and irRC criteria)
- Availability of tumor tissue biopsy for biomarker analysis. Archival tissue can be
used. Fine-needle aspirates will not be acceptable.
- Subjects who meet the following criteria:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥100 x 10^9/L
- Serum creatinine ≥ 1.5 x upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) ≥ 3 x upper limit of normal (ULN) (If there is Liver
Metastasis ≥ 5 x upper limit of normal (ULN))
- Total bilirubin≥1.5 x upper limit of normal (ULN)
- Life expectancy of ≥ 12 weeks on C1D1
- Provision of written informed consent prior to any study specific procedures
Exclusion Criteria:
- Patients who harboring EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK)
rearrangement will not be eligible for this trial.
- Patients who have received more than 3 lines of prior systemic therapy, including
cytotoxic agent or targeted agent
- Previous treatment with immune oncologic agents
- Any major operation or irradiation within 4 weeks of baseline disease assessment
- Subjects with symptomatic central nervous system (CNS) metastases who are
neurologically unstable or have required increasing doses of steroids within the 2
weeks prior to study entry to manage CNS symptoms
- Subjects with history of leptomeningeal metastasis
- Other co-existing malignancies or malignancies diagnosed within the last 3 years with
the exception of basal cell carcinoma or cervical cancer in situ. Any cured cancer
that is considered to have no impact in PFS and OS for the current NSCLC such as
thyroid cancer.
- Subjects with an uncontrolled major cardiovascular disease (including AMI within 12
months, unstable angina within 6 months, over NYHA class III congestive heart failure,
congenital long QT syndrome (Corrected QT (QTcF) >470 ms using Fridericia's correction
on the screening ECG), 2° or more AV Block and uncontrolled hypertension)
- Pregnant or lactating female
- Evidence of any other significant clinical disorder or laboratory finding that makes
it undesirable for the patient to participate in the study
- History of severe hypersensitivity reactions to other monoclonal antibodies, which in
the opinion of the investigator may pose an increased risk of serious infusion
reaction.
- Active, known or suspected autoimmune disease or a documented history of autoimmune
disease, including ulcerative colitis and Crohn's disease (Patients with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll).
- Patient has history of interstitial lung disease or interstitial pneumonitis,
including clinically significant radiation pneumonitis (i.e., affecting activities of
daily living or requiring therapeutic intervention).
- Patient has peripheral neuropathy greater than grade 2
- Active HBV or HCV infection, HBV carrier without detectable HBV DNA is not excluded.
- Known history of testing positive for Human Immunodeficiency Virus (HIV) infection
- Any medical condition that would, in the investigator's judgment, prevent the
patient's participation in the clinical study due to safety concerns, compliance with
clinical study procedures or interpretation of study results.
- Patients requiring chronic treatment with systemic steroid therapy or any
immunosuppressive therapy, other than replacement-dose steroids in the setting of
adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steoids are not
prohibited.
- Use of any live vaccines against infectious disease within 4 weeks of initiation of
study treatment.
- Women of child-bearing potential, unless they are using highly effective methods of
contraception during dosing and for 150 days after the last dose of study treatment.
- Sexually active males unless they use a condom during treatment and for 150 days after
stopping study treatment .
