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

• Status: Unknown status
• Trial end date: 2021-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Royal Marsden NHS Foundation Trust
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

1. Patients should be ≥18 years old on the day of signing the informed consent.

2. Patients must have a histological or cytological diagnosis of NSCLC.

3. Patients should have non-radically treatable stage IIIB or IV disease.

4. Patients must have measurable disease as assessed by RECIST v1.1.

5. 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.

6. Patient should have an ECOG performance status 0-1.

7. Patients should be able to tolerate a course of stereotactic radiotherapy as assessed by the investigator.

8. Patients should have disease within the lung, away from critical structures, suitable for treatment to part of a lesion with lung SBRT.

9. 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%

10. Demonstrate adequate organ function (based on bloods within 10 days of C1D1).

11. Have provided tissue from an archival tissue sample or newly obtained tissue sample.

12. 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.

13. 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.

14. 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.

15. Be willing to provide informed consent for the trial.

Exclusion Criteria:

1. 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.

2. Patients who have received prior chemotherapy, targeted small molecule therapy or radiotherapy within 4 weeks prior to the first dose of pembrolizumab.

3. 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.

4. 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.

5. 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).

6. 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.

7. Patients who have had previous radiotherapy to the lung or other neighbouring region that would preclude the safe administration of lung SBRT.

8. 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).

9. Patients with evidence of additional malignancy that is progressing or requires active treatment.

10. 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.

11. Patients with psychiatric or substance abuse disorders that would interfere with patient's participation.

12. 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.

13. Patients with a history of HIV, HIV 1/2 antibodies, Hepatitis B or Hepatitis C.

14. Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment.

15. Patients with known hypersensitivity to the active substance pembrolizumab or to any of the excipients listed in the SmPC.