PembRolIzuMab and Stereotactic Body Radiotherapy In Metastatic Non-small-cell lunG Cancer Patients

NCT03436056 | Terminated Phase 1 Results DMC

• 1 other identifier: 4590
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single centre non-randomised open label phase 1 trial of lung SBRT to part of a lung lesion in patients with advanced NSCLC in combination with pembrolizumab. This study will recruit up to 24 patients whose lung cancer has progressed beyond one line of palliative chemotherapy, and an EGFR or ALK inhibitor if an EGFR driver mutation or ALK gene rearrangement is present, respectively, and now requires further palliative systemic treatment.

Conditions

Metastatic Non-small-cell lunG Cancer

Keywords

Non-small-cell lunG cancer; NSCLC; metastatic; pembrolizumab; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Dose Limiting Toxicity

  Proportion of all treated patients who have experience at least one Dose Limiting Toxicity (DLT). DLT is assessed using NCI CTCAE v4.0 and defined as any one or more of: neutropenia with fever grade \>=3; thrombocytopenia with bleeding grade \>=3; any grade \>=3 non-haematological toxicity which is definitely, probably, or possibly related to the trial treatment.

  From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT

Secondary Outcomes (10)

• Acute Toxicity Rate

  From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT

• Late Toxicity Rate

  Assessed at start of each 21 day pembrolizumab cycle, starts from 12 weeks after last fraction of lung SBRT and ends 28 days after last on-trial dose of pembrolizumab (treatment ended at disease progression for all trial patients), up to 6 months

• Overall Response Rate

  Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression (occurred no later than 7 months from start of treatment for all patients)

• Disease Control Rate

  Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression (occurred no later than 7 months from start of treatment for all patients)

• Overall Response Rate (irRECIST)

  Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression, start of new anti-cancer treatment, death or end of study

Study Arms (3)

Dose escalation cohort - DOSE LEVEL 1

OTHER

Intervention: One dose pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks.

Radiation: Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#); Drug: Pembrolizumab

Dose escalation cohort - DOSE LEVEL 2

OTHER

Intervention: One dose of pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks.

Radiation: Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#); Drug: Pembrolizumab

Part B - Expansion cohort

OTHER

Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks.

Radiation: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose; Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks.

Also known as: Keytruda

Dose escalation cohort - DOSE LEVEL 1; Dose escalation cohort - DOSE LEVEL 2; Part B - Expansion cohort

Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) RADIATION

Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3

Dose escalation cohort - DOSE LEVEL 1

Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) RADIATION

Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3

Dose escalation cohort - DOSE LEVEL 2

Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose RADIATION

Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3

Part B - Expansion cohort

Eligibility Criteria

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

You may qualify if:

• Patients should be ≥18 years old on the day of signing the informed consent.
• Patients must have a histological or cytological diagnosis of NSCLC.
• Patients should have non-radically treatable stage IIIB or IV disease.
• Patients must have measurable disease as assessed by RECIST v1.1.
• Patients must have had disease progression or be intolerant of standard first line palliative chemotherapy for non-small cell lung cancer. If they are known to have a driver mutation for which there is a small molecule targeted therapy, they must have had disease progression or be intolerant of this.
• Patient should have an ECOG performance status 0-1.
• Patients should be able to tolerate a course of stereotactic radiotherapy as assessed by the investigator.
• Patients should have disease within the lung, away from critical structures, suitable for treatment to part of a lesion with lung SBRT.
• Patients must have adequate organ function including MRC dyspnoea score \<3 and adequate baseline lung function tests, with an FEV1 \> 0.8L or \>30% of predicted and a TLCO \> 30%
• Demonstrate adequate organ function (based on bloods within 10 days of C1D1).
• Have provided tissue from an archival tissue sample or newly obtained tissue sample.
• Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication (C1D1). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Be willing to provide informed consent for the trial.

You may not qualify if:

• Patients who have taken any investigational medicinal product or have used an investigational device within 4 weeks of the first dose of pembrolizumab. Patients may participate in additional observational studies.
• Patients who have received prior chemotherapy, targeted small molecule therapy or radiotherapy within 4 weeks prior to the first dose of pembrolizumab.
• Patients with a diagnosis of immunodeficiency or be receiving systemic steroid therapy (\>7.5 mg of prednisone / \>1 mg of dexamethasone or their equivalent dose) or any other form of immunosuppressive therapy within 7 days prior to the first dose.
• Patients with evidence of 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 who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Patients with evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided the brain metastases are stable and there is no evidence of new or enlarging brain metastases.
• Patients who have had previous radiotherapy to the lung or other neighbouring region that would preclude the safe administration of lung SBRT.
• Patients with evidence of interstitial lung disease, or history of pneumonitis (including non-infectious pneumonitis) that required steroids, or current pneumonitis (including non-infectious pneumonitis).
• Patients with evidence of additional malignancy that is progressing or requires active treatment.
• Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound trial results, interfere with the patient's participation or is not in the best interest of the patient.
• Patients with psychiatric or substance abuse disorders that would interfere with patient's participation.
• Patients who are pregnant / breastfeeding or expecting to conceive within the duration of the trial, starting with the screening visit through 120 days after the last dose.
• Patients with a history of HIV, HIV 1/2 antibodies, Hepatitis B or Hepatitis C.
• Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment.
• Patients with known hypersensitivity to the active substance pembrolizumab or to any of the excipients listed in the SmPC.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Radiosurgery; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

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

priming.trial@rmh.nhs.uk

(+44) 02089156666

Study Officials

• Fiona McDonald, MD

  Royal Marsden NHS Foundation Trust

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Dose Escalation phase with 2 dose levels followed by an Expansion phase

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 19, 2018
• Study Start: March 1, 2018
• Primary Completion: July 8, 2019
• Study Completion: July 8, 2019
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)