Phase 2 Trial of Pembrolizumab in Combination with Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799)

Phase 1

• Conditions: nresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code 10029519Term: Non-small cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000714-37-PL
• Lead Sponsor: Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-01
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 216

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. 4.Have provided tumor 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 tumor 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:
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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified