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

NCT03307759 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: SABRseq
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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.

  Up to 24 months after commencement of treatment

Secondary Outcomes (6)

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

  Assessed up to 24 months

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

  Assessed up to 24 months

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

  Assessed up to 24 months

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

  Assessed up to 24 months

• Percentage of Participants With Overall Survival

  24 months

Study Arms (2)

SABR plus pembrolizumab

ACTIVE COMPARATOR

SABR followed by pembrolizumab

Drug: Pembrolizumab; Radiation: Radiotherapy (SABR)

Pembrolizumab plus SABR

ACTIVE COMPARATOR

Pembrolizumab followed by SABR after cycle 1

Drug: Pembrolizumab; Radiation: Radiotherapy (SABR)

Interventions

Pembrolizumab DRUG

Pembrolizumab

Pembrolizumab plus SABR; SABR plus pembrolizumab

Radiotherapy (SABR) RADIATION

Radiotherapy

Pembrolizumab plus SABR; SABR plus pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Related Links

• National Cancer Institute CTCAE version 4.03 criteria.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Radiotherapy; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Research Development and Operations
• Organization: Peter MacCallum Cancer Centre

crdo@petermac.org

+61 3 8559 5000

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 12, 2017
• Study Start: December 7, 2017
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2022
• Last Updated: September 15, 2025
• Results First Posted: September 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)