Niet-kleincellige longkanker Lung Cancer Non-Small Cell Lung Cancer
Conditions
Interventions
In this study the patient will undergo the experimental treatment of
Pembrolizumab (IV infusion) (Q3W regimen) + SBRT or be part of the control
group placebo (IV infusion) (Q3W regimen) + SBRT
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Has previously untreated NSCLC diagnosed by histology or cytology and confirmed as Stage I or II (T1 to limited T3, N0, M0) 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. Note: participants with pericardium invasion, >2 nodules or 2 nodules that cannot be treated in one field (>2 cm apart and/or total planned target volume [PTV] >163 cc) and diaphragm elevation suggestive of phrenic nerve invasion are excluded. 2. Cannot undergo thoracic surgery due to existing medical illness(es) or anatomically unresectable tumor as determined by the site*s multidisciplinary tumor board. Medically operable participants who decide to treat with SBRT as definitive therapy rather than surgery are also eligible, if patient*s unwillingness to undergo surgical resection is clearly documented. 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 an ECOG performance status of 0, 1, or 2. 4. Is able to receive SBRT and does not have an ultra-centrally located tumor as defined in the radiation manual. 5. Has adequate organ function as defined in Table 2 of protocol. 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 7. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of radiotherapy: • Refrain from donating sperm PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception, unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel*s review of the participant*s medical records, medical examination, or medical history interview) as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP (see Section 10.5) who is not currently pregnant. Note: Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed. Female participants: 8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: •is not a WOCBP OR - is a WOCBP and using a contraceptive method that is highly effective (with a
Exclusion criteria
Exclusion criteria: The participant must be excluded from the study if the participant: 1. Is a WOCBP who has a positive highly sensitive pregnancy test within 24 hours for urine or 72 hours for serum prior to randomization or treatment allocation (see Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: If 24 hours for urine or 72 hours for serum have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative in order for participant to start receiving study medication. 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 coinhibitory T-cell receptor (eg, 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 intervention. 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 and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Refer to Section 6.5 for information on COVID-19 vaccine. 5. Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention administration. 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. A prior NSCLC that occurred and was treated curatively at least 2 years prior to the date of the current diagnosis would be considered a separate primary lung cancer, and therefore an additional malignancy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 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. Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. 11. Has an active autoimmune disease that has required systemic treatment in past 2 years,except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid). 12. Has an active in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective: To compare the Event-free Survival (EFS). Endpoint: EFS: The time from randomization to an event defined as local, regional, or distant recurrence of the treated NSCLC or death from any cause. Objective: To compare Overall Survival (OS). Endpoint: OS: The time from randomization to death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective: To compare the time to death or distant metastases. Endpoint: Time to death or distant metastases: The time from randomization to the first documented distant metastases or death from any cause, whichever occurs first. Objective: To evaluate the safety and tolerability of SBRT + pembrolizumab. Endpoint: Adverse events and Study intervention discontinuations due to AEs Objective: To compare the change from baseline scores in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning scale. Endpoint: Change from baseline scores, calculated for the following scales/items at a pre-specified time point: global health status/QoL (EORTC QLQ-C30 Items 29 and 30), cough (EORTC QLQ-LC13 Item 1), chest pain (EORTC QLQ-LC13 Item 10), dyspnea (EORTC QLQ-C30 Item 8), and physical functioning (EORTC QLQ-C30 Items 1-5). | — |
Countries
Netherlands
Outcome results
None listed