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Non-small Cell Lung CancerPhase 1SABRseqNCT03307759

Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma

A Phase 1 study testing Pembrolizumab and Radiotherapy (SABR) in people with Non-small Cell Lung Cancer, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This investigator driven Phase Ib study will examine the safety, efficacy and biological effects of two schedules of pembrolizumab, an antibody targeted against anti-programmed cell death 1 (PD-1), which will be given either before or after stereotactic ablative body radiotherapy (SABR) for metastatic NSCLC. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Pembrolizumab and Radiotherapy (SABR)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteAustralia
Study dates
7 Dec 2017to 31 Jan 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have provided written informed consent for the trial.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have at least one lesion not planned for SABR that is measurable disease based on RECIST 1.1.
  • Patients must have a histologically or cytologically confirmed metastatic non-small cell lung cancer.
  • Patients with disease previously untreated with systemic therapy must have ≥ 50% PD-L1 staining and patients who have previously received systemic therapy must have ≥ 1% PD-L1 staining on immunohistochemistry
  • Patients must have at least 1-3 lesions suitable for treatment with stereotactic radiotherapy.
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  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumour lesion where feasible. Newly-obtained is defined as a specimen obtained up to 12 weeks prior to randomisation. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient safety concern) may submit an archived specimen only upon agreement from the study principal investigators.
  • Have a performance status of 0-1 on the ECOG Performance Scale (see Appendix 1).
  • Demonstrate adequate organ function as defined in table 3 below, all screening labs should be performed within 10 days of randomisation.
  • Table 3 Adequate Organ Function Laboratory Values
  • Absolute neutrophil count (ANC) ≥1.5x109/L Platelets≥100x109L Haemoglobin ≥90 g/L without transfusion or EPO dependency (within 7 days of assessment)
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥30 mL/min for patients with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT)≤ 2.5 X ULN OR ≤ 5 X ULN for patients with liver metastases
  • International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Life expectancy > 3 months.
  • Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up.
  • Female patient of childbearing potential should have a negative urine or serum pregnancy within 7 days of randomisation. 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 (See Section 8.10). 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.

Who cannot join

  • Has had previous high dose radiotherapy (biological equivalent of >30Gy in 10#) to an area to be treated which includes vertebral bodies (see below).
  • Note: Previous high dose radiotherapy is defined as a biological equivalent dose to above that of 30 Gy in 10 fractions using an alpha/beta ratio (50) of 3.
  • Where a patient has received radiotherapy to an equivalent or lower dose than defined above, stereotactic radiotherapy of the area may be considered. In doing so, assessment of the volume and total dose received by any overlap region must be made, and documented by generating a cumulative plan incorporating both the previous and current treatment fields. It is the treating radiation oncologist's responsibility to review both the current plan and the cumulative plan inclusive of previous radiotherapy.
  • Has had previous thoracic radiotherapy of > 36Gy within the 6 months prior to randomisation.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with small asymptomatic or 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 enlarging brain metastases, and are not using steroids for intracranial neurological symptoms at least 7 days prior to trial randomisation. This exception does not include leptomeningeal disease which is excluded regardless of clinical stability.
  • Has evidence of Spinal Cord Compression.
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  • Has a Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a neurosurgical service and considered stable (see Appendix 2).
  • Requires surgical fixation of bone lesion for stability. All surgical fixation and instrumentation must be completed before randomisation on study.
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of randomisation.
  • Has a diagnosis of immunodeficiency.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has a hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to randomisation or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has diagnosed and/or treated additional malignancy within 5 years prior to randomisation with the exception of: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively treated early stage cervical cancer, breast cancer or prostate cancer with no evidence of active disease. Other exceptions may be considered following consultation with the principal investigator
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has had any systemic anti-cancer therapy or radiation therapy within 4 weeks prior to randomisation
  • Has known interstitial lung disease
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of randomisation. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu- Mist®) are live attenuated vaccines, and are not allowed. -

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

Other trials in Australia

About this study

This investigator driven Phase Ib study will examine the safety, efficacy and biological effects of two schedules of pembrolizumab, an antibody targeted against anti-programmed cell death 1 (PD-1), which will be given either before or after stereotactic ablative body radiotherapy (SABR) for metastatic NSCLC.

Being tested
Pembrolizumab, Radiotherapy (SABR)
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Pembrolizumab

  • Radiotherapy (SABR)Radiation

    Radiotherapy

Study groups in NCT03307759
Study groupRoleWhat they receive
SABR plus pembrolizumabActive comparatorSABR followed by pembrolizumab
Receives: Drug: Pembrolizumab; Radiation: Radiotherapy (SABR)
Pembrolizumab plus SABRActive comparatorPembrolizumab followed by SABR after cycle 1
Receives: Drug: Pembrolizumab; Radiation: Radiotherapy (SABR)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Events Measured Using CTCAE Version 4.03

    Number of participants with grade 3 treatment related adverse events as determined using CTCAE version 4.03 criteria. Grade 3 treatment-related events are high grade toxicities.

    Measured: Up to 24 months after commencement of treatment

Secondary outcomes (6)

  1. Number of Participants With Overall Response (CR + PR) Assessed Using RECIST 1.1

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Assessed up to 24 months

  2. Number of Participants With Overall Response (irCR + irPR) Assessed Using irRECIST

    Per Response Evaluation Criteria In Solid Tumors Criteria (irRECIST) for all lesions and assessed by CT: irComplete Response (CR), Disappearance of all target lesions; irPartial Response (PR), >=30% decrease in TMTB; Overall Response (OR) = irCR + irPR.

    Measured: Assessed up to 24 months

  3. Number of Participants With Overall Response (CMR + PMC) Assessed Using PERCIST1.0

    Per PERCIST 1.0 Criteria for all lesions and assessed by PET/CT: Complete Metabolic Response (CMR), complete resolution of 18F-FDG uptake; Partial Metabolic Response (PMR), >=30% decrease in target measurable tumour 18F-FDG SUL peak; Overall Response (OR) = CMR + PMR.

    Measured: Assessed up to 24 months

  4. Number of Participants With Overall Response (CMRv + PMRv) Assessed Using Peter Mac Metabolic Response Criteria

    Per Peter Mac Metabolic Response Criteria In Solid Tumors Criteria (irRECIST) for a lesion and assessed by PET/CT: Complete Metabolic Response (CMRv), FDG activity within tumour site decreased to equal or less than adjacent soft tissue; Partial Metabolic Response (PMRv), any appreciable reduction in intensity of tumour FDG update or in tumour volume; Overall Response (OR) = CMRv + PMRv.

    Measured: Assessed up to 24 months

  5. Percentage of Participants With Overall Survival

    From randomisation until the date of death from any cause assessed up to the date when the last patient has their 24 months assessment

    Measured: 24 months

  6. Percentage of Participants With Progression Free Survival (PFS)

    From randomisation until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 12 months assessment

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2017
  2. Study start7 Dec 2017
  3. Primary completion31 Jan 2022
  4. Study completion31 Jan 2022

Why it stopped: Slow patient accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03307759
Sponsor's protocol ID
SABRseq
Acronym
SABRseq
Status last verified
Aug 2025
First submitted
6 Oct 2017
Last updated
15 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab and Radiotherapy (SABR) in people with Non-small Cell Lung Cancer, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events Measured Using CTCAE Version 4.03 (time frame: Up to 24 months after commencement of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03307759.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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