Phase 3 study of SBRT ± pembrolizumab for participants with medically inoperable Stage I or IIA NSCLC
- Conditions
- on-Small Cell Lung Cancer Stage I or IIAMedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004320-11-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 530
A participant will be eligible for inclusion in the study if the participant:
1. Has NSCLC diagnosed by histology or cytology and confirmed as Stage I or IIA NSCLC (AJCC 8th edition) by chest CT and PET scan. Prospective participants with mediastinal lymph nodes measured on chest CT as >1 cm in the short axis or PET avid lymph nodes may be eligible if the lymph node(s) in question is biopsied and is histologically benign.
2. Cannot undergo thoracic surgery due to existing medical illness(es) as determined by the participant’s treating physician in consultation with the site’s multi-disciplinary tumor board. The recommendation from the tumor board as well as the reason(s) for declaring the patient medically inoperable must be included in the participant’s study documents in order to be eligible for KEYNOTE-867. Patients, who are able to withstand thoracic surgery, but choose to pursue non-operative therapy, are not eligible. If there is no tumor board, then this decision will be made by the investigator in consultation with a thoracic surgeon and a radiation oncologist if the investigator is not a radiation oncologist.
3. Has a ECOG Performance Status of 0, 1, or 2.
4. Is able to receive SBRT.
5. Has adequate organ function. Specimens must be collected within 7 days prior to the start of study intervention.
6. Is male or female =18 years of age, at the time of signing the informed consent.
Male Participants
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female Participants
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) not a women of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance during the treatment interval and for at least 120 days (corresponding to time needed to eliminate any study treatment (pembrolizumab).
8. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400
The participant must be excluded from the study if the participant:
1. Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
3. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or breast. Participants receiving radiotherapy to the contralateral breast at least 5 years prior to randomization may still be eligible.
4. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines are allowed.
5. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
8. Has a known hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
10. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
11. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). However, replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency), while systemic, will be permitted for study eligibility.
12. Has an active infection requiring systemic therapy.
13. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
14. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). No TB testing is required unless mandated by local health authority.
15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
16. Has a known psychiatric or subs
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: 1.To compare the Event Free Survival (EFS).<br> 2.To compare Overall Survival (OS).<br> ;<br> Secondary Objective: 1.To compare the time to death or distant metastases (TDDM).<br> 2.To evaluate the safety and tolerability of Stereotactic Body Radiotherapy (SBRT) + pembrolizumab (MK-3475).<br> 3.To compare the change from baseline scores in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning scale.<br> ;<br> Primary end point(s): 1. Event-Free Survival (EFS)<br> 2. Overall Survival (OS)<br> ;<br> Timepoint(s) of evaluation of this end point: 1. Up to approximately 6 years<br> 2. Up to approximately 6 years<br>
- Secondary Outcome Measures
Name Time Method