Metastatic Non-small-cell lunG CancerPhase 1PRIMINGNCT03436056
PembRolIzuMab and Stereotactic Body Radiotherapy In Metastatic Non-small-cell lunG Cancer Patients
A Phase 1 study testing Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#), Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) and Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose in people with Metastatic Non-small-cell lunG Cancer, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Non-small-cell lunG Cancer
- What is being tested?
- Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#), Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) and Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2018to 8 Jul 2019
- 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
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
About this study
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.
Read the detailed description
The study will be conducted in two parts; an initial lung SBRT dose escalation phase (Part A), followed by a lung SBRT dose expansion cohort (Part B). The dose escalation phase is based on a 3+3 design such that patients will be treated in cohorts of 3-6 patients. A maximum of 12 patients will be allocated to one of two doses of lung SBRT in combination with pembrolizumab to determine the MTD, DLTs and RP2D. If there is more than one DLT in cohort 1, this treatment combination will be deemed as being unacceptable, and it would lead to termination of the study. Note, there is no de-escalation in cohort 1. During the dose expansion cohort, 12 patients will have lung SBRT dosed at the RP2D determined during the dose escalation phase in combination with pembrolizumab to obtain additional safety and response data. Maintenance pembrolizumab will continue until disease progression, unacceptable toxicities, the patient withdraws consent to the trial, or the patient has completed 24 months of treatment. A maximum of 24 patients will be treated in the study.
All patients will receive pembrolizumab on cycle (C) 1 day (D) 1, in Part A and B of the study. All patients will receive lung SBRT on C1D15, C1D17, and C1D19 as per lung SBRT protocol (See Appendix 3). Although C1D1 can occur +/- 3 days, C1D15, C1D17, and C1D19, must be scheduled for a Monday, Wednesday and Friday, respectively. Patients in part A will receive lung SBRT dosed at 30 Gy in 3# in cohort 1, or 54 Gy in 3# in cohort 2. Patients in Part B will receive the RP2D of lung SBRT, determined in Part A. All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks, until disease progression, unacceptable toxicities, the patient withdraws consent from the trial, or the patient has completed 24 months of treatment.
In the dose escalation phase, a minimum of 3 patients will be required per dose level being assessed. A minimum gap of 1 week will be left between the treatment of the first and the second, and between the second and the third patients with the combination of pembrolizumab and lung SBRT to mitigate against multiple patients suffering from acute toxicity. The DLT period for this study is 12 weeks from the last dose of lung SBRT (i.e. at C6D1). The dose escalation will be considered by the Safety Review Committee (SRC) once the 3rd or 6th patient in the cohort has completed the DLT period. If no DLT is observed at a dose level, then lung SBRT will be dose escalated to the next dosing level (see Table 1). If 1 out of 3 patients experience a DLT, then the cohort will be expanded to 6 patients. If 1 in 6 patients experience a DLT, then the dose will be escalated to the next dosing level. However, if ≥ 2 in 6 patients experience a DLT then the maximum administered dose (MAD) will have been reached, and the RP2D will be the previous dosing level that will be used for the dose expansion cohorts. If the MAD is seen at dose level 1 then the study will be terminated. While waiting for 3 or 6 patients to complete the DLT period, no additional patients will be recruited. Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort and taken a decision to dose escalate to the next cohort or expand the current cohort to 6 patients.
Once the MTD has been determined the trial enters the dose expansion phase (unless the MTD is dose level 1). Here, 12 patients will be treated with the RP2D of SBRT combined with pembrolizumab.
If there is ongoing clinical benefit at 24 months, the CI/PI will need to discuss with the sponsor and MSD, on a case by case basis for the continuation of pembrolizumab.
- Conditions
- Metastatic Non-small-cell lunG Cancer
- Being tested
- Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#), Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#), Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose, Pembrolizumab
- Keywords
- Non-small-cell lunG cancer, NSCLC, metastatic, pembrolizumab, radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#)Radiation
Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3
Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#)Radiation
Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3
Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated doseRadiation
Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3
PembrolizumabDrug
Also called Keytruda
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Radiation: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT
Secondary outcomes (10)
Acute Toxicity Rate
Percentage of patients any acute toxicity, by worst grade as assessed using CTCAE v4.0
Measured: From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT
Late Toxicity Rate
Percentage of patients with any late toxicity, by worst grade as assessed using CTCAE v4.0
Measured: 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
Count of patients with best overall response of complete or partial response at any time, assessed using RECIST v1.1
Measured: 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
Count of patients with best overall response at any time of complete or partial response, or stable disease, assessed by RECIST v1.1
Measured: 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)
Count of patients with best response of complete or partial response, assessed using Immune Related Response Criteria (irRC) as defined by: Wolchok JD et al. Guidelines for the evaluation of immune therapy activity in solid tumors: Immune related response criteria. Clin Cancer Res 2009;15(23):7412. (72)
Measured: 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
Frequency of PD-1/PD-L1 Expression
PD-1/PD-L1 expression distribution in responders and non-responders
Measured: Response to be defined as per previous endpoint, PD1/PD-L1 to be measured at study entry
Overall Survival at Six Months
Count of patients known to be alive at six months
Measured: 6 months after last dose of lung SBRT
Overall Survival at 12 Months
Count of patients known to be alive at 12 months
Measured: 12 months after last dose of lung SBRT
Progression Free Survival at 6 Months
Count of patients known to be alive and free from progression at 6 months
Measured: 6 months after last dose of lung SBRT
Progression Free Survival at 12 Months
Count of patients known to be alive and free from progression at 12 months
Measured: 12 months after last dose of lung SBRT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start1 Mar 2018
- Primary completion8 Jul 2019
- Study completion8 Jul 2019
Why it stopped: funding pulled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Non-small-cell lunG CancerStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose Escalation phase with 2 dose levels followed by an Expansion phase
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Fiona McDonald, MD, Study chair, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03436056
- Sponsor's protocol ID
- 4590
- Acronym
- PRIMING
- Status last verified
- Jan 2026
- First submitted
- 16 Jan 2018
- Last updated
- 29 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PembRolIzuMab and Stereotactic Body Radiotherapy In Metastatic Non-small-cell lunG Cancer Patients
- ClinicalTrials.gov ID
- NCT03436056
- Acronym / sponsor ID
- PRIMING / 4590
- Conditions
- Metastatic Non-small-cell lunG Cancer
- Keywords
- Non-small-cell lunG cancer, NSCLC, metastatic, pembrolizumab, radiotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: funding pulled
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 8 Jul 2019 (actual)
- Study completion
- 8 Jul 2019 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Posted 29 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study will be conducted in two parts; an initial lung SBRT dose escalation phase (Part A), followed by a lung SBRT dose expansion cohort (Part B). The dose escalation phase is based on a 3+3 design such that patients will be treated in cohorts of 3-6 patients. A maximum of 12 patients will be allocated to one of two doses of lung SBRT in combination with pembrolizumab to determine the MTD, DLTs and RP2D. If there is more than one DLT in cohort 1, this treatment combination will be deemed as being unacceptable, and it would lead to termination of the study. Note, there is no de-escalation in cohort 1. During the dose expansion cohort, 12 patients will have lung SBRT dosed at the RP2D determined during the dose escalation phase in combination with pembrolizumab to obtain additional safety and response data. Maintenance pembrolizumab will continue until disease progression, unacceptable toxicities, the patient withdraws consent to the trial, or the patient has completed 24 months of treatment. A maximum of 24 patients will be treated in the study.
All patients will receive pembrolizumab on cycle (C) 1 day (D) 1, in Part A and B of the study. All patients will receive lung SBRT on C1D15, C1D17, and C1D19 as per lung SBRT protocol (See Appendix 3). Although C1D1 can occur +/- 3 days, C1D15, C1D17, and C1D19, must be scheduled for a Monday, Wednesday and Friday, respectively. Patients in part A will receive lung SBRT dosed at 30 Gy in 3# in cohort 1, or 54 Gy in 3# in cohort 2. Patients in Part B will receive the RP2D of lung SBRT, determined in Part A. All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks, until disease progression, unacceptable toxicities, the patient withdraws consent from the trial, or the patient has completed 24 months of treatment.
In the dose escalation phase, a minimum of 3 patients will be required per dose level being assessed. A minimum gap of 1 week will be left between the treatment of the first and the second, and between the second and the third patients with the combination of pembrolizumab and lung SBRT to mitigate against multiple patients suffering from acute toxicity. The DLT period for this study is 12 weeks from the last dose of lung SBRT (i.e. at C6D1). The dose escalation will be considered by the Safety Review Committee (SRC) once the 3rd or 6th patient in the cohort has completed the DLT period. If no DLT is observed at a dose level, then lung SBRT will be dose escalated to the next dosing level (see Table 1). If 1 out of 3 patients experience a DLT, then the cohort will be expanded to 6 patients. If 1 in 6 patients experience a DLT, then the dose will be escalated to the next dosing level. However, if ≥ 2 in 6 patients experience a DLT then the maximum administered dose (MAD) will have been reached, and the RP2D will be the previous dosing level that will be used for the dose expansion cohorts. If the MAD is seen at dose level 1 then the study will be terminated. While waiting for 3 or 6 patients to complete the DLT period, no additional patients will be recruited. Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort and taken a decision to dose escalate to the next cohort or expand the current cohort to 6 patients.
Once the MTD has been determined the trial enters the dose expansion phase (unless the MTD is dose level 1). Here, 12 patients will be treated with the RP2D of SBRT combined with pembrolizumab.
If there is ongoing clinical benefit at 24 months, the CI/PI will need to discuss with the sponsor and MSD, on a case by case basis for the continuation of pembrolizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Dose Escalation phase with 2 dose levels followed by an Expansion phase
| Arm | Type | Receives |
|---|---|---|
| Dose escalation cohort - DOSE LEVEL 1 | Other | Radiation: Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#), Drug: PembrolizumabIntervention: 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. |
| Dose escalation cohort - DOSE LEVEL 2 | Other | Radiation: Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#), Drug: PembrolizumabIntervention: 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. |
| Part B - Expansion cohort | Other | Radiation: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose, Drug: PembrolizumabIntervention: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#)Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3 | Radiation | Dose escalation cohort - DOSE LEVEL 1 |
| Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#)Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3 | Radiation | Dose escalation cohort - DOSE LEVEL 2 |
| Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated doseStereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 | Radiation | Part B - Expansion cohort |
| PembrolizumabAlso: KeytrudaPembrolizumab 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. | Drug | Dose escalation cohort - DOSE LEVEL 1, Dose escalation cohort - DOSE LEVEL 2, Part B - Expansion cohort |
Primary outcome
Proportion of Patients With Dose Limiting Toxicity
Time frame: From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT
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.
10 secondary outcomes
Acute Toxicity Rate
Time frame: From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT
Late Toxicity Rate
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Frequency of PD-1/PD-L1 Expression
Time frame: Response to be defined as per previous endpoint, PD1/PD-L1 to be measured at study entry
Overall Survival at Six Months
Time frame: 6 months after last dose of lung SBRT
Overall Survival at 12 Months
Time frame: 12 months after last dose of lung SBRT
Progression Free Survival at 6 Months
Time frame: 6 months after last dose of lung SBRT
Progression Free Survival at 12 Months
Time frame: 12 months after last dose of lung SBRT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fiona McDonald, MD study chair
Royal Marsden NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#), Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) and Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose in people with Metastatic Non-small-cell lunG Cancer, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
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 15 inclusion and 15 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 29 Jan 2026. 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 United Kingdom. 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 29 Jan 2026). 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?
Proportion of Patients With Dose Limiting Toxicity (time frame: From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jan 2026.