Pembrolizumab and Palliative Radiotherapy in Lung

NCT02587455 | Completed Phase 1 Results DMC

• 1 other identifier: CCR 4282
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Lung cancer is the second most common cancer in the UK with around 43,500 new patients diagnosed each year. About 69% of patients are diagnosed with advanced stage disease and at present these patients would be expected to survive for less than 12 months. These statistics therefore show the need for the development of new effective drugs in the treatment of advanced Lung cancer. Recent trial results have shown the efficacy of immunotherapy in treating several types of tumours including lung cancer. These tumours are known to express a high level of a glycoprotein called PDL1 which is a component of the PD1 pathway. In cancer the PD1 pathway can be hijacked by tumours leading to the immune system being suppressed. The aim of the new drug Pembrolizumab is to restart the PD1 pathway and use the immune system to help fight the cancer cells. Radiotherapy has also been shown to cause cancer to increase production of the proteins that can block the immune system. Therefore it has been proposed that combine of new immunotherapy agent such as pembrolizumab and radiotherapy in the treatment of lung cancer will allow more cancer cells to be killed through the immune system. The purpose of this study is to see if pembrolizumab can safety be combined with standard palliative radiotherapy in patients with lung cancer. In addition once the patients have completed their course of radiotherapy they will remain on pembrolizumab alone and the study will look at how well this treatment regimen can control the growth of the cancer.

Conditions

Thoracic Tumours

Keywords

Non-small cell carcinoma

Outcome Measures

Primary Outcomes (2)

• Toxicity Rate of Dose Limiting Toxicities (DLTs) Assessed by CTCAEv4

  DLT period is defined as the interval of 2 months following the final fraction of RT (at the beginning of cycle 4), using CTCAE v4.0 for acute toxicity. For this study a DLT would be regarded as any event of pneumonitis at ≥ grade 2. DLTs were collected to determine the Maximum-Tolerated Dose (MTD). The toxicity rate will be stated as the proportion of patients who have had a DLT calculated with a 95% confidence interval.

  2 months following the final fraction of RT

• Maximum Tolerated Dose (MTD) of Pembrolizumab That Can be Safely Combined With Radiotherapy (RT) in the Absence of Dose Limiting Toxicity (DLT) Assessed by CTCAEv4

  MTD was determined by testing increasing doses of pembrolizumab (100mg / 200mg) and low/high doses of RT. MTD reflects the highest dose in the absence of a DLT. The DLT period is defined as the interval of 2 months following the final fraction of RT (at the beginning of cycle 4), using CTCAE v4.0 for acute toxicity. For this study a DLT would be regarded as any event of pneumonitis at ≥ grade 2.

  2 months following the final fraction of RT

Secondary Outcomes (7)

• Progression Free Survival at 6 and 12 Months

  6 and 12 months

• Overall Survival at 6 and 12 Months

  6 and 12 months

• PFS at 6 and 12 Months by PDL-1 Status (Strong vs Non-strong)

  6 and 12 months

• OS at 6 and 12 Months by PDL-1 Status (Strong vs Non-strong)

  6 and 12 months

• Progression Free Survival (PFS2) From Date of First Response at 6 and 12 Months

  6 and 12 months

Study Arms (2)

Low Dose Radiotherapy Arm

EXPERIMENTAL

Pembrolizumab and radiotherapy

Drug: Pembrolizumab; Radiation: Radiotherapy

High Dose Radiotherapy Arm

EXPERIMENTAL

Pembrolizumab and radiotherapy

Drug: Pembrolizumab; Radiation: Radiotherapy

Interventions

Pembrolizumab DRUG

Pembrolizumab - Trial Treatment

Also known as: MK-3475/pembrolizumab (KEYTRUDA®)

High Dose Radiotherapy Arm; Low Dose Radiotherapy Arm

Radiotherapy RADIATION

Radiotherapy - Standard Treatment

High Dose Radiotherapy Arm; Low Dose Radiotherapy Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Have measurable disease based on RECIST 1.1.
• Histologically verified NSCLC including squamous cell carcinoma, adenocarcinoma, adenosquamous or large cell anaplastic carcinoma; requiring palliative radiotherapy for which no curative therapy exists will be recruited into the trial.
• Patients are permitted to have extrathoracic disease which will not be encompassed in the radiotherapy field. This disease will be assessed for abscopal response
• Ability to tolerate a course of palliative radiotherapy to the lung.
• Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumour lesion.
• Have a performance status of 0-2 on the ECOG Performance Scale.
• Demonstrate adequate organ function, all screening labs should be performed within 10 days of confirmation of eligibility.
• Patient's lung function tests at baseline should have an FEV1 \> 0.8L or \> 30%.
• See protocol section.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Previous radiotherapy to the lung
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• Has an 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. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require the use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, noninfectious pneumonitis.
• Has received prior therapy with an antiPD1, antiPDL1, antiPDL2, antiCD137, or anti Cytotoxic T-lymphocyte associated antigen4 (CTLA4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
• See protocol section.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator
• Institute of Cancer Research, United Kingdom: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (2)

NIHR Biomedical Research Centre at RM and ICR (https://www.cancerbrc.org/)

London, SW3 6JJ, United Kingdom

Location

NIHR Biomedical Research Centre at RM and ICR (https://www.cancerbrc.org/)

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Interventions

pembrolizumab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: PEAR Trial Manager
• Organization: The Royal Marsden NHS Foundation Trust

Pear.Trial@rmh.nhs.uk

+442089156666

Study Officials

• Dr Merina Ahmed

  Consultant Clinical Oncologist

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 27, 2015
• Study Start: June 24, 2016
• Primary Completion: August 20, 2021
• Study Completion: August 20, 2021
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Locations

GB (2)