Pembrolizumab in Patients With Non-Small Cell Lung Cancer and a Performance Status 2 (PePS2)

• ClinicalTrials.gov Identifier: NCT02733159
• Recruitment Status: Active, not recruiting
• First Posted: April 11, 2016
• Last Update Posted: November 18, 2022
• Sponsor: University of Birmingham
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): University of Birmingham

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: pembrolizumab	Phase 2

Detailed Description:

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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Pembrolizumab in Patients With Non-small Cell Lung Cancer and a Performance Status of 2
• Actual Study Start Date: November 7, 2016
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: January 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab; Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.	Drug: pembrolizumab; anti PD-1; Other Name: MK-3475

Outcome Measures

Primary Outcome Measures :

1. Toxicity - Treatment Related Dose Delay or Treatment Discontinuation [ Time Frame: Through study completion, a maximum of 2 years and 6 months after end of treatment ]
   Adverse events will be recorded in relation to each cycle of treatment and graded according to CTCAE criteria. The toxicity co-primary outcome measure for the trial is defined as the occurrence of a treatment-related dose delay or treatment discontinuation due to toxicity.
2. Efficacy - Durable Clinical Benefit [ Time Frame: ≥18 weeks, up to maximum of 2 years ]
   Patients will have CT scans every 9 weeks from baseline until disease progression. On each occasion, overall tumour burden will be assessed using RECIST version 1.1. The efficacy co-primary outcome measure for the trial is durable clinical benefit defined as the occurrence of CR, PR or SD without prior progressive disease at or after the second scheduled CT scan (scheduled to occur at 18 weeks).

Secondary Outcome Measures :

1. Objective Response [ Time Frame: ≥18 weeks, up to maximum of 2 years ]
   Objective response (OR) is the occurrence of CR or PR as the best overall response. OR will be based on responses confirmed using the subsequent 9-weekly scan but OR based on unconfirmed responses will also be reported.
2. Health Related Quality of Life [ Time Frame: Through study completion, up to a maximum of 2 years ]
   This is defined as the functional effect of a medical condition and/or its consequent treatment upon a patient. The purpose of Health Related Quality of Life (HRQoL) measurement is to quantify the degree to which the medical condition or its treatment impacts the individual's life in a valid and reproducible way. HRQoL will be assessed over time using FACT-L questionnaire and EQ-5D questionnaire.
3. Time to Progression [ Time Frame: Time to progression up to 2 years ]
   This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded. Patients with no recorded progression at the time of analysis or who die without recorded progression will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.
4. Progression-free Survival Time [ Time Frame: Progression-free survival time up to 2 years ]
   This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression. Patients who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.
5. Overall Survival Time [ Time Frame: Survival time up to 2 years or date of death ]
   This is defined as the time from commencement of trial treatment to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive.
6. Duration of Objective Response and Duration of Stable Disease [ Time Frame: Survival time up to 2 years or date of death ]
   This is defined as the time from commencement of trial treatment to the date of the subsequent CT scan when progressive disease is first confirmed or date of death without previously recorded progression. This outcome is calculated and reported separately for patients who achieve an OR or SD. Patients experiencing OR or SD who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Core Inclusion Criteria:

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

Contacts and Locations

Locations

United Kingdom

The Christie NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom, M20 4BX

Southampton University Hospitals NHS Trust

Southampton, Hampshire, United Kingdom, SO16 6YD

Maidstone and Tunbridge Wells NHS Trust

Maidstone, Kent, United Kingdom, ME16 9QQ

University Hospital Birmingham NHS Foundation Trust

Birmingham, West Midlands, United Kingdom, B15 2TH

Velindre Cancer Centre

Cardiff, United Kingdom, CF14 2TL

Western General Hospital

Edinburgh, United Kingdom

United Lincolnshire Hospitals NHS Trust

Lincoln, United Kingdom, LN2 5QY

Barts Health NHS Trust

London, United Kingdom, E1 1BB

University College London Hospitals

London, United Kingdom, NW1 2BU

The Royal Marsden Hospital

London, United Kingdom, SW3 6JJ

Sponsors and Collaborators

University of Birmingham

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Gary Middleton, Professor; University of Birmingham

More Information

Study Data/Documents: Trial Website 

Publications of Results:

Middleton G, Brock K, Savage J, Mant R, Summers Y, Connibear J, Shah R, Ottensmeier C, Shaw P, Lee SM, Popat S, Barrie C, Barone G, Billingham L. Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Lancet Respir Med. 2020 Sep;8(9):895-904. doi: 10.1016/S2213-2600(20)30033-3. Epub 2020 Mar 19.

• Responsible Party: University of Birmingham
• ClinicalTrials.gov Identifier: NCT02733159
• Other Study ID Numbers: RG_14-172; 2015-002241-55 ( EudraCT Number ); ISRCTN10047797 ( Registry Identifier: ISRCTN Registry )
• First Posted: April 11, 2016
• Last Update Posted: November 18, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Birmingham:

Performance Status 2; Pembrolizumab; MK-3475

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action