Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10029519 Term: Non-small cell lung cancer stage III 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, unresectable, pathologically confirmed NSCLC and Stage IIIA, IIIB or IIIC NSCLC by American Joint Committee on Cancer Version 8. 2. No evidence of metastatic disease by whole body PET/ CT scan, diagnostic quality CT scan, and brain imaging. The process for image collection and transmission to the central imaging vendor can be found in the Site Imaging Manual. 3. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. 4. Have provided tumour tissue sample (core, incisional, or excisional biopsy). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. In cases where the core, incisional, or excisional biopsy is not available or cannot be obtained due to anatomical location of tumour or medical condition of the participant, a cell block obtained through EUS/EBUS may be submitted after consultation with the Sponsor Clinical Director and documenting approval via a Sponsor Communication Form. 5. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. Have adequate pulmonary function test (PFT) as a forced expiratory volume in 1 second (FEV1) >50% of predicted normal volume and the carbon monoxide lung diffusing capacity (DLCO) >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if their resting capillary/arterial blood gas on room air reveals an oxygen pressure (PO2) >60 mmHg. 7. Have adequate organ function 8. A male participant must agree to use contraception for at least 180 days after the last dose of study treatment in Cycles 1 through 3 or for 120 days after the last dose of study treatment in Cycle 4 through the end of treatment and refrain from donating sperm during this period. 9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and if participant is a woman of childbearing potential (WOCBP), agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment in Cycles 1 through 3 or for 120 days after the last dose of study treatment in Cycle 4 through the end of treatment. 10. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However participant may participate in the main trial without participating in Future Biomedical Research. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 151
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 2. Has small cell lung cancer. Mixed tumors will be categorized by the predominant cell type: if small cell elements are present, the participant is ineligible; if non-small cell histology with any squamous element is present (example squamous, adenosquamous), the participant is not eligible for Cohort B (pemetrexed based chemotherapy). 3. Has had documented weight loss >10% in the preceding 3 months. 4. Participants whose radiation treatment plans are likely to encompass a volume of whole lung receiving >20 Gy in total (V20) of more than 31% of lung volume. 5. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus or for breast cancer. 6. 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 co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). 7. Has received a live vaccine within 30 days prior to the first dose of study 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 (e.g., FluMist®) are live attenuated vaccines and are not allowed. 8. Has had an allogenic tissue/solid organ transplant. 9. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. 10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg prednisone daily or equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. 11. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. 12. Has severe hypersensitivity (Grade 3 or higher) to pembrolizumab and/or any of its excipients (refer to the IB for a list of excipients). 13. Has a known severe hypersensitivity (Grade 3 or higher) to any of the study chemotherapy agents and/or to any of their excipients. 14. 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. 15. Has a history of (non-infectious) pneumonitis/ interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease that requires steroids. 16. Has an active infection requiring systemic therapy. 17. Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority. 18. 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. 19. Has a known history of active tuberculosis (TB; Bacillus tuberculosis) 20. Has a history or current e
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Within each platinum doublet chemotherapy cohort, evaluate the percentage of participants who develop Grade 3 or higher pneumonitis 2. Within each platinum doublet chemotherapy cohort, estimate the objective response rate as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;Secondary Objective: 1. Within each platinum doublet chemotherapy cohort, evaluate the progression-free survival (PFS) assessed by BICR according to RECIST v.1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ 2. Within each platinum doublet chemotherapy cohort, evaluate overall survival (OS) 3. Within each platinum doublet chemotherapy cohort, evaluate the safety and tolerability of each treatment regimen by the percentage of participants who develop AEs;Primary end point(s): - Grade 3 or higher pneumonitis - Confirmed complete response or partial response;Timepoint(s) of evaluation of this end point: Tumor imaging to evaluate efficacy endpoints that include Complete Response and Partial Response will be performed every 9 weeks (± 7 days) until Week 54 and then every 12 weeks (± 14 days) until Week 150 and then every 24 weeks (± 28 days). KN799 will use a sequential monitoring procedure based on pre-specified criteria described in the Statistical Analysis Plan in the protocol to monitor the safety and efficacy endpoints. There will likely be multiple interim analyses for each cohort of the study. The first interim analysis will be conducted when at least 36 participants have completed a minimum of 15 weeks of follow-up in either cohort. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PFS defined as the time from enrollment to the first documented local recurrence or distant metastasis or death due to any cause, whichever occurs first - OS defined as the time from enrollment to death due to any cause - Adverse events (AEs) - Discontinuations due to AEs;Timepoint(s) of evaluation of this end point: Tumor imaging to evaluate efficacy endpoints that include PFS will be performed every 9 weeks (± 7 days) until Week 54 and then every 12 weeks (± 14 days) until Week 150 and then every 24 weeks (± 28 days). OS and safety endpoints will be monitored during the treatment Phase at clinic visits scheduled every 3 weeks (± 3 days), or by telephone contact conducted as needed. During the survival follow-up period, participants will be contacted every 12 weeks (± 14 days) to assess survival status. | — |
Countries
Australia, France, Germany, Korea, Republic of, New Zealand, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme (UK) Ltd.
Outcome results
None listed