Pembrolizumab in Patients With Non-Small Cell Lung Cancer and a Performance Status 2

A Phase II Trial of Pembrolizumab in Patients With Non-small Cell Lung Cancer and a Performance Status of 2

This study is to determine that pembrolizumab is safe and tolerable at the selected dose for the treatment of Non-Small Cell Lung Cancer (NSCLC) in patients with a performance status of 2. All patients will receive pembrolizumab.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. There are several studies which demonstrate a role for the immune system in fighting lung cancer. However, there are multiple mechanisms by which cancer dampens this response. The PD-1 receptor-ligand interaction is one of the major pathways hijacked by tumours to help evade detection and elimination by the cells of the immune system. A number of compounds which block this pathway, including the drug pembrolizumab, have shown impressive results in some patients.

At present all of the trials with pembrolizumab reported thus far have been in patients with a good Performance Status (PS) of 0-1, a measure of daily activity. Unfortunately many patients with lung cancer have impaired performance status, making them ineligible for trials of new therapies including anti PD-1. Clinical trials of standard-of-care therapy have been successfully performed in the PS=2 only population demonstrating the feasibility of performing clinical trials in this population.

In this trial, the investigators would like to determine whether this drug can be used to treat Performance status 2 patients with a lower general daily activity. The purpose of this trial is to determine that pembrolizumab is safe and tolerable. The investigators would also like to see how well the treatment works, find out more information about tumour shrinkage, and learn more about the disease and how it changes over time.

Core Inclusion Criteria:

• Histologically confirmed PD-L1 status defined NSCLC. Biopsy must be within 70 days of first treatment with pembrolizumab.

• Eastern Cooperative Oncology Group (ECOG) performance status 2.

• Life expectancy > 12 weeks.

• Uni-dimensionally measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

• Computerised Tomography (CT) scan of chest and abdomen within 28 days of starting pembrolizumab.

• Adequate haematological function:

  • Platelet count ≥100 x 109 /L.
  • Neutrophils ≥1.5 x 109/L.
  • Haemoglobin ≥ 90 g/L.

• Adequate hepatic function:

  • Serum bilirubin ≤1.5 x upper limit of normal (ULN).
  • Serum transaminases ≤2.5 x ULN.

• Adequate renal function: Creatinine clearance <1.5 times ULN concurrent with creatinine clearance >50 ml/min.

• Provision of signed and dated, written informed consent prior to any trial specific procedures, sampling and analyses.

Core Exclusion Criteria:

• Patients who do not meet the criteria of performance status = 2 on the ECOG Performance scale.
• Untreated symptomatic brain or leptomeningeal metastatic disease.
• Medical or psychiatric conditions compromising informed consent.
• Any medical condition which in the opinion of the investigator would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol.
• Radiotherapy within 28 days of trial treatment.
• Active autoimmune disease that has required systemic treatment in past 2 years
• Chronic usage of steroids or other immunosuppressant medication.
• Previous history of pneumonitis.
• Any evidence of clinical autoimmunity.