PALACE: Cemiplimab Trial According to ctDNA Levels

This is an open-label, non-randomised, phase II, multicenter clinical trial. The total sample size is 63 patients. The population to be included are stage IV or stage IIIB/C not candidates for definitive chemo/radiotherapy or surgical resection non-small cell lung cancer (NSCLC) per the 8th edition TNM with no prior systemic anti-cancer therap.

Patients will be treated with Cemiplimab for 2 cycles and after response evaluation and ctDNA levels analysis, patients will be treated with Cemiplimab plus chemotherapy or cemiplimab monotherapy depending on response and ctDNA levels.

The primary research goal is to determine whether therapy decision making based on ctDNA analysis improves overall survival.

Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 4-6 months. An estimated treatment period of 2 years, 2 years of follow-up and the preparation of the final report and the close out visit are expected to extend the study duration to a total of 6.5 years.

Inclusion criteria

• Histologically confirmed stage IV or stage IIIB/C not candidates for definitive chemo/radiotherapy or surgical resection non-small cell lung cancer (NSCLC) per the 8th edition TNM with no prior systemic anti-cancer therapy
• PDL1 ≥50%
• ECOG performance status 0-1
• Patients aged ≥ 18 years
• Prior adjuvant or neoadjuvant chemotherapy for early stage is permitted if completed at least 6 months prior to enrolment
• Presence of at least one measurable lesion by CT-scan per RECIST version 1.1
• Anticipated life expectancy >12 weeks
• Correct hematological, hepatic and renal function
• Patient consent must be obtained in the appropriate manner as established in the applicable local and regulatory requirements
• Patients must be accessible for treatment and follow-up
• Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 3 days before enrolment.
• All sexually active men and women of childbearing potential must use a highly effective contraceptive method during the study treatment and for a period of at least 4 months following the last administration of trial drugs

Exclusion criteria

• Patients whose tumors harbor an activating mutation in EGFR, ALK translocation, or ROS Proto-Oncogene 1 (ROS1) rearrangements sensitive to available targeted inhibitor therapy
• Patients with grade ≥2 neuropathy
• Pregnant or breastfeeding women
• Patients with a weight loss >10% within the previous 3 months
• Patients with carcinomatous meningitis
• Patients with a history of other malignant diseases within the past 3 years
• Patients must have recovered from a major surgery at least 14 days prior to enrolment
• Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol
• Prior treatment with antineoplasic drugs or thoracic radiotherapy for any reason different from the ones specific in the inclusion criteria
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease less than 6 months before enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy
• Patients with a combination of small cell lung cancer and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma
• Has known allergy or hypersensitivity to components of study drug
• Significant comorbidities that preclude the administration of chemotherapy according to the investigator's criteria
• Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
• Untreated brain metastasis(es) that may be considered active
• Immunosuppressive corticosteroid doses within 4 weeks prior to the first dose of cemiplimab
• Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus; or diagnosis of immunodeficiency
• History of interstitial lung disease or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
• History of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments
• Patients with a history of solid organ transplant
• Receipt of live vaccines within 30 days of first study treatment
• Women of childbearing potential, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 4 months after the last dose.