Adjuvant treatment for elderly or unfit patients with stage III lung cancer

Who can take part

• Adults aged 18 or older
• Diagnosed with stage III non-small cell lung cancer that cannot be removed with surgery
• Considered unfit for standard treatment due to age or other health conditions
• Able to start chemotherapy and radiation therapy
• Not previously treated for this lung cancer with immunotherapy or chemotherapy
• Have certain blood and organ function within normal limits
• No active autoimmune disease or other serious medical conditions
• Not pregnant or breastfeeding
• Willing to use contraception during the study and for 6 months after
• Covered by French national health insurance
• Able to provide informed consent and comply with the study schedule
• ECOG performance status of 0-1
• Not have certain genetic mutations (EGFR, ALK, ROS1)
• Have a PD-L1 test result available
• No evidence of metastatic disease or brain metastases
• No history of radiation to the chest
• No other cancer in the past 3 years (except for certain non-melanoma skin cancers)
• Have adequate respiratory function as assessed by pulmonary function tests
• Have acceptable hematologic, renal, and hepatic function
• No active infection or recent severe infection
• No recent surgery or live vaccine within the specified period
• No history of solid organ or bone marrow transplant
• No other experimental treatments within the last 30 days
• No condition that would interfere with study participation or safety
• No active substance abuse or mental health condition that would affect ability to participate in the study
• No known allergy to cemiplimab or its components
• No history of interstitial lung disease or pulmonary fibrosis
• No significant cardiovascular disease (e.g., recent heart attack, uncontrolled hypertension)
• No autoimmune disorders requiring systemic treatment
• No organ transplantation history
• No serious medical condition that could interfere with the study
• No known positivity for HIV, hepatitis B, or hepatitis C
• No major surgery within 4 weeks prior to study start
• No prior participation in this trial
• No guardianship or legal incapacity
• No geographical or social factors that would prevent follow-up visits
• Be able to understand the study procedures and give informed consent
• Previously had a PD-L1 expression level assessed by the investigator center
• No known contraindication to the study drugs or treatments
• No history of severe side effects from other anti-cancer drugs
• No withdrawal of blood donation during the study period
• No excessive sun exposure without protection
• Avoid becoming pregnant or fathering a child during the study and for 6 months after treatment
• No use of certain live vaccines within 14 days prior to starting the study treatment
• Be willing to adhere to all requirements of the study protocol
• Not be simultaneously enrolled in another interventional trial
• Not have any other condition that, in the opinion of the investigator, could compromise the study's objectives or the safety of the patient
• Have a high probability of being able to complete the study as planned
• Have a life expectancy of at least 3 months
• Be able to swallow and retain oral medication
• No known active liver disease or cirrhosis
• No active severe infection
• No history of pneumonitis that required steroids
• No live vaccines within 30 days of starting study treatment
• No known allergy to the study drugs or their excipients
• No use of systemic corticosteroids (more than 10 mg/day of prednisone or equivalent) or other immunosuppressive drugs within 7 days prior to starting study treatment (with exceptions)
• No prior treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer
• No prior radiation therapy to the chest area.
• No other active medical condition that would preclude study participation.
• Have histologically or cytologically confirmed stage IIIA/B/C non-small cell lung cancer that is not resectable
• Be considered eligible for treatment with sequential chemoradiotherapy as per multidisciplinary team decision
• Have at least one measurable lesion according to RECIST 1.1 criteria
• Have adequate respiratory function defined as FEV1 >= 40% and DLCO >= 40% of predicted values.
• Have acceptable bone marrow function as defined by ANC >= 1.5 x 10^9/L, platelets >= 100 x 10^9/L, and hemoglobin >= 9 g/dL.
• Have adequate renal and hepatic function as defined by creatinine clearance >= 45 mL/min, bilirubin <= 1.5 x ULN, AST/ALT <= 3 x ULN, and albumin >= 28 g/L.
• Provide written informed consent before any study-specific procedures are performed.
• Be aged 70 years or older with an ECOG PS of 0-1, OR be younger than 70 with a Charlson comorbidity score of at least 3.
• Have a negative pregnancy test (if female of childbearing potential) and agree to use effective contraception during treatment and for 6 months after the last dose of study drug.
• Be negative for known activating EGFR mutations and ALK/ROS1 translocations.
• Have no contraindication to receiving cemiplimab, chemotherapy, or radiation therapy as per the investigator's judgment.
• Have no other active malignancy requiring treatment within the last 3 years except for non-melanoma skin cancer or cervical cancer in situ.
• Have no history of active autoimmune disease or other conditions requiring systemic immunosuppressive therapy.
• Have no history of interstitial lung disease or active pneumonitis.
• Have no active severe infection requiring systemic therapy within the last 4 weeks.
• Have no evidence of severe systemic disease (e.g., autoimmune disorders, active infections) or psychiatric illness that would interfere with the patient's ability to comply with study requirements.
• Have no clinical signs of worsening respiratory function or significant cardiovascular disease within the past 3 months.
• Have no signs of acute or chronic infection that would affect the safety of the patient or the integrity of the study results.
• Have no history of organ allografts or active bleeding diatheses.
• Have no condition that would compromise the safety of the patient or the integrity of the study.
• Patients must have a contraindication to chemoradiation as per the multidisciplinary team.
• Patients may be enrolled if they meet all other criteria.
• Have a life expectancy of at least 6 months
• Be willing to undergo genetic testing for PD-L1 expression and discuss the results with their doctor.
• Compliance with study procedures is essential for the validity of the study.
• Patients should be informed of the benefits and risks of participating in the study.
• Patients must have a negative serum pregnancy test at screening (for women of childbearing potential).
• Male patients with a partner of childbearing potential must use an effective birth control method during the study and for 6 months after the last dose of study drug