A Phase 3, Randomized, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Stereotactic Body Radiotherapy (SBRT) with or without Pembrolizumab (MK-3475) in Participants with Unresected Stage I or II Non-Small Cell Lung Cancer (NSCLC) (KEYNOTE-867)
- Conditions
- iet-kleincellige longkankerLung CancerNon-Small Cell Lung Cancer10038666
- Registration Number
- NL-OMON52095
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 6
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Objective: To compare the Event-free Survival (EFS).<br /><br>Endpoint: EFS: The time from randomization to an event defined as local,<br /><br>regional, or distant recurrence of the treated NSCLC or death from any cause.<br /><br><br /><br>Objective: To compare Overall Survival (OS).<br /><br>Endpoint: OS: The time from randomization to death from any cause.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Objective: To compare the time to death or distant metastases.<br /><br>Endpoint: Time to death or distant metastases: The time from randomization to<br /><br>the first documented distant metastases or death from any cause, whichever<br /><br>occurs first.<br /><br><br /><br>Objective: To evaluate the safety and tolerability of SBRT + pembrolizumab.<br /><br>Endpoint: Adverse events and Study intervention discontinuations due to AEs<br /><br><br /><br>Objective: To compare the change from baseline scores in global health<br /><br>status/quality of life (QoL), cough, chest pain, dyspnea, and physical<br /><br>functioning scale.<br /><br>Endpoint: Change from baseline scores, calculated for the following<br /><br>scales/items at a pre-specified time point: global health status/QoL (EORTC<br /><br>QLQ-C30 Items 29 and 30), cough (EORTC QLQ-LC13 Item 1), chest pain (EORTC<br /><br>QLQ-LC13 Item 10), dyspnea (EORTC QLQ-C30 Item 8), and physical functioning<br /><br>(EORTC QLQ-C30 Items 1-5).</p><br>