PDR001 in Patients With Non-small Cell Lung Cancer Harboring KRAS/NRAS Mutation or no Actionable Genetic Abnormalities

This is an interventional treatment trial for Cancer Read More

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 .