Chemo +/- Pembrolizumab (MK-3475) as Perioperative Therapy for Stage II, IIIA-Resectable IIIB (N2) NSCLC
- Conditions
- eoadjuvant/Adjuvant treatment for participants with Resectable Stage II or IIIA-B (N2) NSCLCMedDRA version: 21.1Level: PTClassification code 10029518Term: Non-small cell lung cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10029520Term: Non-small cell lung cancer stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001832-21-IE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 786
1. Male/female participants who are at least 18 years of age on the day
of signing informed consent with previously untreated and pathologically
confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC. Lymph node
disease requires pathologic confirmation, while T3 (rib destruction)
disease requires only radiographic documentation. A PET scan may be
utilized as a surrogate for pathologic staging of N1 lymph nodes for
participants with T2b and T4 tumors (the presence or absence of tumor
in the N1 lymph nodes will not change the actual stage by which the
participant is stratified). Similarly, biopsy confirmation of N2 disease is
not required for pathologically confirmed T3N1 tumors and T4N0-1
tumors, as knowledge of the N2 status will not change the stage.
2. Be able to undergo protocol therapy, including necessary surgery.
3. If male, agrees to the following during the intervention period and for
at least the time needed to eliminate each study intervention after the
last dose of study intervention. The length of time required to continue
contraception for each study intervention is as follows:
- Chemotherapy: 95 days
• Refrains from donating sperm
PLUS either:
• Abstains from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis) and agrees to
remain abstinent
OR
• Uses 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:
*Uses a male condom plus partner use of an additional contraceptive
method when having penile-vaginal intercourse with a WOCBP who is
not currently pregnant. .
*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
4. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP
OR
• A WOCBP and:
* Uses a contraceptive method that is highly effective (with a failure rate
of <1% per year), with low user dependency, or be abstinent from
heterosexual intercourse as their preferred and usual lifestyle (abstinent
on a long-term and persistent basis), during the intervention period and
for at least the time needed to eliminate each study intervention after
the last dose of study intervention and agrees not to donate eggs (ova,
oocytes) to others or freeze/store for her own use for the purpose of
reproduction during this period. The length of time required to continue
contraception for each study intervention is as follows:
-Chemotherapy: 180 days
-MK-3475: 120 days
The investigator should evaluate the potential for contraceptive method
failure (ie, noncompliance, recently initiated) in relationship to the first
dose of study intervention. Contraceptive use by women 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.
- Has a negative highly sensitive pregn
1. Has one of the following tumor locations/types:
- NSCLC involving the superior sulcus
- Large cell neuro-endocrine cancer (LCNEC)
- Sarcomatoid tumor
2. Has a history of (non-infectious) pneumonitis /interstitial lung
disease that required steroids or has current pneumonitis/interstitial
lung disease that requires steroids.
3. Has an active infection requiring systemic therapy.
4. Has had an allogenic tissue/solid organ transplant.
5. Has a known severe hypersensitivity (= Grade 3) to pembrolizumab,
its active substance and/or any of its excipients.
(Refer to the respective Investigator'sBrochure for a list of excipients.)
6. Has a known severe hypersensitivity (= Grade 3) to any of the study
chemotherapy agents and/or to any of their excipients.
7. Has an active autoimmune disease that has required systemic
treatment in past 2 years (ie, with use of disease modifying agents,
corticosteroids or immunosuppressive drugs). Replacement therapy (eg,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency) is not considered a form of systemic
treatment and is allowed.
8. Has a known history of human immunodeficiency virus (HIV)
infection. No HIV testing is required unless mandated by local health
authority.
9. 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.
10. Has a known history of active tuberculosis (TB; Bacillus
tuberculosis).
11. Has a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the trial,
interfere with the participant's participation for the full duration of the
trial, or is not in the best interest of the participant to participate, in the
opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would
interfere with cooperating with the requirements of the trial.
13. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2
agent or with an agent directed to another co inhibitory T-cell
receptor (eg, CTLA-4, OX-40, CD137).
14. Has received prior systemic anticancer therapy including
investigational agents for the current malignancy prior to
randomization/allocation.
15. Has received prior radiotherapy within 2 weeks of start of trial
treatment. Participants must have recovered from all radiation-related
toxicities, not require corticosteroids, and not have had radiation
pneumonitis.
16. Has received a live or live attenuated vaccine within 30 days prior to
the first dose of trial 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 and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not
allowed.
17. Is currently participating in or has participated in a trial of an
investigational agent or has used an investigational device within 4
weeks prior to the first dose of trial treatment.
18. Has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy (dose exceeding 10 mg daily of prednisone equivalent) or any
other form of immunosuppressive therapy within 7 days prior the first
dose of trial drug.
19. Has a known additio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method