Immunotherapeutic treatment with Pembrolizumab (antibody) in patients with early stage non-small cell lung cancer

Phase 1

• Conditions: Stage IB (T = 4 cm), II and IIIA NSCLC; MedDRA version: 19.1Level: 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: EUCTR2015-000575-27-CZ
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-20
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1380

Inclusion Criteria

- Pathological diagnosis of NSCLC confirmed at surgery, any histology is eligible;
- Confirmed UICC v7 stage IB with T = 4 cm, II-IIIA NSCLC after complete surgical resection (lobectomy, sleeve lobectomy, bi-lobectomy or pneumonectomy) as documented in the pathology report;
- Resection margins proved microscopically free (R0); Resection margins should be considered to be the bronchial, venous and arterial stumps, peribronchial soft tissue, any peripheral margin near the tumor or of additionally resected tissue;
- A systematic nodal dissection is recommended or at least a lobespecific systematic nodal dissection. However, the intraoperative lymph node evaluation can be accepted if no lymph nodes are found in those area and there is clear documentation in the operative report by the surgeon of exploration of the required lymph node areas. At minimum, the pathology and/or operative report should include the examination of at least two different mediastinal nodal (N2) station with one being subcarinal (level 7);
- No extracapsular nodal extension of the tumor;
- The highest mediastinal node removed can be positive
- Carcinoma in situ can be present at bronchial margin
- Availability of tumor sample obtained at surgical resection for PD-L1 Immunohistochemistry (IHC) expression assessment.
- At least 18 years;
- Written informed consent must be given according to ICH/GCP, and national/local regulations;
- Adjuvant chemotherapy is not mandatory but considered for patients with stage IB (T = 4 cm) and strongly recommended for stage II and IIIA, and will be administered according to national and local guidelines. Patients who received more than 4 cycles of adjuvant therapy are not eligible;
- ECOG Performance status 0-1;
- Adequate organ function performed within 10 days of treatment initiation;
- Female patients with childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study medication)
- If of childbearing potential, female patients must be willing to use two adequate barrier methods throughout the study, starting with the screening visit up to 120 days after last dose of chemotherapeutic and investigational agents as specified in the protocol;
- Male patients with a female partner(s) of child-bearing potential must agree to use two adequate barrier methods throughout the trial starting with the screening visit through 120 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
- Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 120 days after the last study treatment;
- Absence of severe comorbidities that in the opinion of the Investigator might hamper the participation to the study and/or the treatment administration
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 815
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 565

Exclusion Criteria

- Evidence of disease at clinical examination and/or baseline radiological assessment on baseline assessment as documented by contrast enhanced chest/upper abdomen CT scan, brain CT/MRI and clinical examination within 8 weeks prior to the randomization date;
- Prior or foreseen neoadjuvant or adjuvant radiotherapy and/or neoadjuvant chemotherapy;
- Prior treatment with an anti-PD-1, anti-PD-L1/2, anti- CD137, CTLA-4 modulators; patients receiving live vaccine within 30 days prior to the first dose of study treatment are not eligible;
- Current participation in a interventional clinical trial or treatment with an investigational agent or use of an investigational device within 4 weeks of the first dose of study treatment;
- Known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive). Known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg results. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay;
- Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 3 days prior to the first dose of trial treatment;
- History of interstitial lung disease (ILD) OR a history of (noninfectious) pneumonitis that required oral or IV steroids (other than COPD exacerbation) or current pneumonitis;
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Any replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Patients with hyperthyroidism or hypothyroidism but that are stable on hormone replacement are also allowed
- History of a hematologic or primary solid tumor malignancy, unless in remission for at least 5 years. A pT1-2 prostatic cancer Gleason score <6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix is eligible;
- Previous allogeneic tissue/solid organ transplant;
- Active infection requiring therapy;
- Surgery or chemotherapy related toxicity (toxicity resolved to grade 1 (see Appendix D), with the exception of alopecia, fatigue, neuropathy and lack of appetite /nausea)

Study & Design

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