A Clinical Trial of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer Patients

A Phase II Clinical Trial Evaluating the Safety and Efficacy of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Patients With Eastern Cooperative Oncology Group (ECOG) Performance Status of 2

This is a single-arm phase II clinical trial evaluating the safety and efficacy of the PD-L1 inhibitor durvalumab as first-line therapy in 47 patients with advanced NSCLC and ECOG Performance Status 2 (PS2).

Durvalumab will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Durvalumab will be administered at 1500 mg (fixed dose) every 4 weeks until disease progression, death, unacceptable toxicity or withdrawal of consent for a maximum of 12 months of therapy.

Inclusion Criteria:

• Written informed consent

• Patients must have histologically or cytologically confirmed Stage IIIB or IV (American Joint Committee on Cancer, 7th edition; AJCC 7) non-small cell lung cancer.

• Patients must have measurable disease.

• Patients must have not have received any prior therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) for the treatment of stage IV NSCLC.

• Age ≥ 18 years at time of study entry.

• ECOG performance status of 2.

• Life expectancy of greater than 12 weeks.

• Tissue available (archived or fresh tumor biopsy) for the PD-L1 assay.

• Patients must have normal organ and marrow function as defined below:

  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤ 5x ULN Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula

• Female subjects must either be of non-reproductive potential OR must have a negative serum pregnancy test upon study entry.

• The effects of durvalumab on the developing human fetus are unknown. For this reason and because immunomodulatory agents are potentially teratogenic, sexually active women of child-bearing potential and men must agree to use adequate contraception (2 methods of effective contraception from screening) from screening, for the duration of study participation, and for at least 90 days following the last infusion of durvalumab.

• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

• Involvement in the planning and/or conduct of the study; previous enrollment in the present study.
• Participation in another clinical study with an investigational product for cancer during the last 12 months.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids in excess of prednisone 10 mg/d or equivalent.
• Sensitizing mutations in EGFR or rearrangements in ALK or ROS1.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab.
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids . Patients may be on systemic corticosteroids provided the dose does not exceed prednisone 10 mg/d or equivalent for 1 week prior to study drug administration.
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant.
• Uncontrolled intercurrent illness.
• Known history of previous clinical diagnosis of tuberculosis.
• History of leptomeningeal carcinomatosis.
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
• Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
• Subjects with uncontrolled seizures.
• Pregnant women; breastfeeding should be discontinued.
• Prior history of radiation pneumonitis.