Immunotherapy in addition to standard chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). A multicenter single-arm phase II study.

Germany, Switzerland (ICTRP)

ICTRP Trial ID
NCT02572843 (ICTRP)

Official title (approved by ethics committee)
Anti-PD-L1 antibody MEDI4736 in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC). A multicenter single-arm phase II trial. (BASEC)

Academic title
Anti-PD-L1 Antibody MEDI4736 in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-small Cell Lung Cancer (NSCLC). A Multicenter Single-arm Phase II Trial. (ICTRP)

Public title
Anti-PD-L1 in Stage IIIA(N2) Non-small Cell Lung Cancer (NSCLC) (ICTRP)

Disease under investigation
NSCLC Non-small Cell Lung Cancer (ICTRP)

Intervention under investigation
Drug: MEDI4736 (anti-PD-L1) (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Gender: All
Maximum age: 75 Years
Minimum age: 18 Years

Inclusion Criteria:

- Written informed consent according to ICH-GCP regulations before patient registration
and any protocol-related procedures.

- Pathologically proven NSCLC (adeno-, squamous-, large cell carcinoma or NSCLC not
otherwise specified) irrespective of genomic aberrations or PD-L1 expression status.

- Tumor tissue is available for the mandatory translational research (preferably
histology, cytology allowed).

- Tumor stage T1-3N2M0 (stage IIIA(N2)) according to the TNM classification, 7th
edition, (October 2009). Mediastinal lymph node staging has to follow the process
chart.

- Tumor is considered resectable based on a multidisciplinary tumor board decision made
before neoadjuvant treatment. Resectable is when a complete resection can be achieved
according to Rami-Porta {Rami-Porta, 2005 #88}.

- Measurable disease according to RECIST 1.1 criteria (non-nodal lesions =10 mm in
longest diameter, lymph nodes =15 mm in short axis) by PET/CT with contrast enhanced
CT-scan.

- WHO performance status 0-1.

- Age 18-75 years at time of registration.

- Appropriate lung function based on the ESTS guidelines {Brunelli, 2009 #19}:

- For pneumonectomy: FEV1 and DLCO =80%. If one of both <80% an exercise test peak
VO2 >75% or 20ml/kg/min is needed,

- For resection less than pneumonectomy (resection up to the calculated extent):
exercise test peak VO2 =35% or =10ml/kg/min, with predicted postoperative FEV1
and DLCO = 30%.

- Adequate hematological values: hemoglobin = 90 g/L, absolute neutrophils count = 1.5 x
109/L, platelets count = 100 x 109/L.

- Adequate hepatic function: bilirubin = 1.5 x ULN, AST/ALT = 1.5 x ULN, AP = 2.5 x ULN.

- Adequate renal function: calculated creatinine clearance = 60 mL/min, according to the
formula of Cockcroft-Gault.

- Women with child-bearing potential are using effective contraception are not pregnant
or lactating and agree not to become pregnant during participation in the trial and
during 90 days after the last treatment. A negative serum pregnancy test performed
within 7 days before registration into the trial is required for all women with
child-bearing potential. Men agree not to father a child during participation in the
trial and during 90 days after the last treatment.

- Patient 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:

- Presence of any distant metastasis or N3 disease. Brain metastases have to be excluded
by CT or MRI.

- Sulcus superior tumors (Pancoast tumors).

- Previous or concomitant malignancy within 5 years prior registration with the
exception of adequately treated localized non-melanoma skin cancer or cervical
carcinoma in situ.

- Any previous treatment for NSCLC.

- Any previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736.

- Previous radiotherapy to the chest.

- Absolute contraindications for the use of corticosteroids as premedication.

- Concurrent treatment with other experimental drugs or other anti-cancer therapy,
treatment in a clinical trial within 30 days prior to registration.

- Current or prior use of immunosuppressive medication within 28 days before the first
dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses (i.e. which must not exceed 10 mg/day
of prednisone or an equivalent corticosteroid) and the premedication for chemotherapy.

- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure
NYHA III or IV, unstable angina pectoris even if medically controlled, history of
myocardial infarction during the last 3 months, serious arrhythmias requiring
medication (with exception of atrial fibrillation or paroxysmal supraventricular
tachycardia).

- Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3
electrocardiograms (ECGs) using Bazett's Correction.

- Preexisting peripheral neuropathy (> grade 1).

- Body weight less than 30 kg.

- Active autoimmune disease requiring systemic treatment within the past 3 months or a
documented history of clinically severe autoimmune disease or a syndrome that requires
systemic steroids or immunosuppressive agents. Exceptions: - Vitiligo or resolved
childhood asthma/atopy - Hypothyroidism stable on hormone replacement or Sjorgen's
syndrome

- Active or prior documented inflammatory bowel disease (e.g. Crohn's disease,
ulcerative colitis).

- Known evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency
virus (HIV) infection.

- History of primary immunodeficiency.

- History of allogeneic organ transplant.

- Known history of previous clinical diagnosis of tuberculosis.

- Receipt of live attenuated vaccination any time during trial therapy with MEDI4736 and
within 30 days of receiving the last dose of MEDI4736.

- Any concomitant drugs contraindicated for use with MEDI4736: this includes systemic
corticosteroids, methotrexate, azathioprine, and tumor necrosis factor (TNF)-a
blockers. Any concomitant drugs contraindicated for use with the other trial drugs
according to the locally approved product information.

- Known hypersensitivity to trial drugs (cisplatin and docetaxel), to the IMP or to any
excipient.

- Any other serious underlying medical (e.g. uncontrolled diabetes mellitus, active
uncontrolled infection, active gastric ulcer, uncontrolled seizures, severe hearing
impairment), psychiatric, psychological, familial or geographical condition that, in
the judgment of the investigator, may interfere with the planned staging, treatment
and follow-up, affect patient compliance or place the patient at high risk from
treatment-related complications.
(ICTRP)

not available

Primary and secondary end points
Event-free survival (EFS) (ICTRP)

Event-free survival (EFS);Overall survival (OS);Objective response (OR) after neoadjuvant chemotherapy;OR after neoadjuvant immunotherapy;Pathological responses (pCR);Adverse Events (AEs) (according to NCI CTCAE v4.0) (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Sacha Rothschild, MD, PhD, University Hospital, Basel, Switzerland (ICTRP)

Secondary trial IDs
000001480, SAKK 16/14 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT02572843 (ICTRP)