AIO-YMO/TRK-0416 (DURATION) is a open-label, treatment stratified and randomized phase II
study of Durvalumab, frail or elderly patients with metastatic non-squamous NSCLC with no
targetable molecular alterations (EGFRwt; ALKtransl-) and not amenable to cisplatinum-based
standard-combination chemotherapy but eligible for at-least mono-chemotherapy with
gemcitabine or vinorelbine.
1. Written informed consent and any locally-required authorization (EU Data Privacy
Directive in the EU) obtained from the subject prior to performing any
protocol-related procedures, including screening evaluations
2. Age ≥ 70 years at time of study entry and/or Charlson-Comorbidity-Index (CCI) >1
and/or Performance status ECOG >1
3. Histologically confirmed diagnosis of metastatic NSCLC and no targetable molecular
alterations (EGFRwt; ALKtransl-) and not amenable to cisplatinum-based
4. Patients with measurable disease (at least one uni-dimensionally measurable target
lesion not previously irradiated, by CT-scan or MRI) according to Response Evaluation
Criteria in Solid Tumors (RECIST 1.1) are eligible.
5. A formalin fixed, paraffin-embedded (FFPE) tumor tissue block (fresh or archival less
than 3 years old or recent) or a minimum of 10 unstained slides of tumor sample
(slices must be less than 90 days old and collected on SuperFrost slides provided by
the sponsor) must be available for biomarker (PD-L1) evaluation. Biopsy should be
excisional, incisional or core needle. Fine needle aspiration is inappropriate.
6. No prior chemotherapy or any other systemic therapy for metastatic NSCLC. Patients who
have received prior platinum-containing adjuvant, neoadjuvant, or definitive
chemoradiation for locally advanced disease are eligible, provided that progression
has occurred >6 months from last therapy.
7. Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery and
palliative radiotherapy for bone pain: 2 weeks) prior to start of treatment and
patient recovered from toxic effects or associated adverse events.
8. Adequate blood count, liver-enzymes, and renal function:
- 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 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) ≤ 2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤ 5x 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
9. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits, examinations including follow up
and appropriate contraception
1. Mixed small-cell lung cancer and NSCLC histology
2. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
electrocardiograms (ECGs) using Fredericia's correction
3. History of another primary malignancy except local prostate cancer without need for
systemic treatment (e.g. active surveillance, operation without need for adjuvant
treatment) and malignancies treated with curative intent and with no known active
disease >2 years befor the first dose of study drug and of low potential risk for
recurrence, e.g. adequately treated non-melanoma skin cancer or lentigo maligna
without evidence of disease, adequately treated carcinoma in situ without evidence of
disease (e.g. cervical cancer in situ)
4. Pre-existing peripheral neuropathy of Grade ≥ 2
5. Brain metastasis or spinal cord compression unless asymptomatic or treated and stable
off steroids and anti-convulsants for at least 1 month prior to study treatement.
6. 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.
7. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
8. History of primary immunodeficiency
9. History of allogeneic organ transplant
10. History of hypersensitivity to durvalumab or any excipient
11. History of hypersensitivity to any of the comparator agents
12. Medication that is known to interfere with any of the agents applied in the trial.
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. Clinical diagnosis of active tuberculosis
15. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab
16. Male patients of reproductive potential who are not employing an effective method of
birth control (failure rate of less than 1% per year)
17. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
18. Participation in another clinical study with an investigational product during the
last 30 days before inclusion
19. Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab
20. 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
21. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) ≤ 21 days prior to the first dose of study
drug or ≤4 half-lifes of the agent administered, which ever comes first.
22. Previous enrollment or randomization in the present study.
23. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff of sponsor and study site)
24. Patient who might be dependent on the sponsor, site or the investigator
25. Patient who has been incarcerated or involuntarily institutionalized by court order or
by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
26. Patients who are unable to consent because they do not understand the nature,
significance and implications of the clinical trial and therefore cannot form a
rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].