Neoadjuvant/Adjuvant treatment for participants with Resectable Stage IIB or IIIA NSCLC MedDRA version: 20.0 Level: PT Classification code 10029518 Term: Non-small cell lung cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: PT Classification code 10029520 Term: Non-small cell lung cancer stage IIIA System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male/female participants who are at least 18 years of age on the day of signing informed consent with previously untreated, histologically confirmed NSCLC and histologically confirmed Stage IIB or IIIA NSCLC. (AJCC Version 8). Lymph node disease requires histologic confirmation, while T3 (rib destruction) disease requires only radiographic documentation. 2. Be able to undergo protocol therapy, including necessary surgery. 3. A male participant must agree to use contraception, as detailed in protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing) for at least 180 days, (corresponding to time needed to eliminate any study treatment(s) [pembrolizumab and or any active combination] plus an additional 90 days [a spermatogenesis cycle] for study treatments where there is risk of clinically relevant genotoxicity) after the last dose of study treatment and refrain from donating sperm during this period. 4. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant. 5. A female participant is eligible to participate if she is not pregnant (see protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing OR b.) A WOCBP who agrees to follow the contraceptive guidance in protocol Appendix 3: Contraceptive Guidance and Pregnancy Testing during the treatment period and for at least 180 days (corresponding to time needed to eliminate any study treatment(s) [pembrolizumab and or any active combination] plus 30 days [a menstruation cycle] for study treatments with risk of genotoxicity) after the last dose of study treatment. 6. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the trial. 7. Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central PD-L1 testing. See Procedures Manual for further details. 8. Have an ECOG performance status of 0 to 1 within 10 days of randomization. 9. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of trial treatment. 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 260 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 526
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment (see protocol Appendix 3). If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 2. Has one of the following tumor locations/types: - NSCLC involving the superior sulcus - Large cell neuro-endocrine cancer (LCNEC) - Sarcomatoid tumor 3. Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids. 4. Has an active infection requiring systemic therapy. 5. Has had an allogenic tissue/solid organ transplant. 6. 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.) 7. Has a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy agents and/or to any of their excipients. 8. 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. 9. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority. 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 a known history of active tuberculosis (TB; Bacillus tuberculosis). 12. 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. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial. 14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). 15. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to randomization/allocation. 16. 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. 17. Has received a live 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. 18. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational devic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate event-free survival (EFS) by biopsy assessed by blinded central pathologist or by imaging using RECIST 1.1 assessed by blinded independent central review (BICR). 2. To evaluate the overall survival (OS).;Secondary Objective: 1. To evaluate the rate of major pathological response (mPR) assessed by blinded central laboratory pathologist following NAC +/- pembrolizumab. 2. To evaluate the rate of pathological complete response (pCR) in the resected primary tumor and lymph nodes assessed by blinded central laboratory pathologist following NAC +/- pembrolizumab. 3. To evaluate mean change from baseline in the neoadjuvant phase and in the adjuvant phase in global health status/quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ)-C30. 4. To evaluate the safety and tolerability of NAC plus pembrolizumab followed by surgery and adjuvant pembrolizumab.;Primary end point(s): - Event-free survival (EFS) - Overall survival (OS);Timepoint(s) of evaluation of this end point: EFS at IA2 and OS at Final Analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Major pathological response (mPR) rate - Pathological complete response (pCR) rate - PRO outcome - Safety and tolerability;Timepoint(s) of evaluation of this end point: mPR and pCR at IA1 | — |
Countries
Argentina, Belgium, Brazil, Canada, France, Germany, Ireland, Italy, Japan, Korea, Republic of, Poland, Romania, Russian Federation, South Africa, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed