Patient case: 68-year-old male with non-small cell carcinoma; genetic feature: MET

Clinical trial: Durvalumab (MEDI4736) With or Without SBRT in Clinical Stage IB and II Non-small Cell Lung Cancer

Summary: The purpose of this study is to find out the effectiveness of the drug durvalumab (MEDI4736) with or without stereotactic body radiation therapy (SBRT) as treatment for stage IB and II non-small cell lung cancer (NSCLC) prior to surgery and one year following surgery.

Detailed description: This is a randomized open label phase II trial of preoperative anti-PD-L1 antibody durvalumab with or without concurrent non-ablative radiation followed by surgical resection and postoperative monthly maintenance durvalumab for twelve months.

Eligibility: Inclusion Criteria:
  1. Patient has histologically or cytologically proven clinical stages IB /II NSCLC and is considered eligible for surgical resection with curative intent.
  2. Tumor amenable to pre-treatment core needle biopsy without unacceptable risk of a major procedural complication.
  3. Measureable disease, as defined by RECIST v1.1.
  4. Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures.
  5. Age > 18 years at time of study entry
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Adequate normal organ and marrow function as defined below:
  -  Haemoglobin ≥ 9.0 g/dL
  -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
  -  Platelet count ≥ 100 x 109/L (>100,000 per mm3)
  -  Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  -  AST (SGOT)/ALT (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN).
  -  Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  Males:
  Creatinine CL (mL/min)=Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)
  Females:
  Creatinine CL (mL/min)=Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL)
  8. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  9. 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.
  10. No prior therapy for their lung cancer. -
  Exclusion Criteria:
  1. Participation in another clinical study with an investigational product during the last 3 weeks.
  2. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
  3. History of another primary malignancy except for:
  -  Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence.
  -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  -  Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer , treated localized prostate cancer and ductal carcinoma-in situ.
  4. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  5. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  6. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
  7. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
  8. 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. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
  9. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  10. History of primary immunodeficiency.
  11. History of allogeneic organ transplant.
  12. History of hypersensitivity to durvalumab or any excipient.
  13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  14. Known history of previous clinical diagnosis of tuberculosis.
  15. History of leptomeningeal carcinomatosis.
  16. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
  17. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
  18. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  19. Subjects with uncontrolled seizures.
  20. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or evidence of active pneumonitis on screening chest CT scan.
  21. Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
  22. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) 30 days prior to the first dose of study drug.

Relevance to patient case: not relevant