Phase 3 study of SBRT ± pembrolizumab for participants with Unresected Stage I or II NSCLC
- Conditions
- on-Small Cell Lung Cancer Stage I or IIAMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004320-11-PL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 530
A participant will be eligible for inclusion in the study if the participant:
1. Has previously untreated NSCLC diagnosed by histology or cytology and confirmed as Stage I or II (T1 limited T3, NO, MO) 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) 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 as defined in the radiation manual.
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
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 failure rate of <1% per year), or be abstinent from heterosexual
intercourse as their preferred and usual lifestyle (abstinent on a longterm
and persistent basis) during the intervention period and for at least
120 days after the last dose of pembrolizumab/placebo and 180 days
after the last radiotherapy dose. The investigator should evaluate the
potential for contraceptive method failure (ie, noncompliance, recently
initiated) in relationship to
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. 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 PDL2
agent or with an agent directed to another stimulatory or coinhibitory
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 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
protocol 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.
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.
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 except replacement therapy (eg thyroxine,
insulin, or physiologic corticosteroid).
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 substance abuse disorder that would
interfere with the participant's ability to cooperate with the
requirements of the study.
17. Is pregnant or breastfeeding or expecting to conceive or father
children within th
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1.To compare the Event Free Survival (EFS).<br>2.To compare Overall Survival (OS).;Secondary Objective: 1.To compare the time to death or distant metastases.<br>2.To evaluate the safety and tolerability of Stereotactic Body Radiotherapy (SBRT) + pembrolizumab .<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.;Primary end point(s): 1. Event-Free Survival (EFS)<br>2. Overall Survival (OS);Timepoint(s) of evaluation of this end point: 1. Up to approximately 58 months<br>2. Up to approximately 65 months<br>
- Secondary Outcome Measures
Name Time Method