Reduced-dose Carboplatin-doublet-chemotherapy + Cemiplimab vs Cemiplimab Monotherapy in Treatment Naive Older and Frail Patients With Metastatic NSCLC With PD-L1 <50%

Inclusion criteria

• Informed Consent as documented by signature
• Histologically or cytologically confirmed NSCLC. Mixed histology with small-cell component is not allowed.
• Metastatic or advanced or recurrent NSCLC without a curative-intent treatment option (surgery or chemo-radiotherapy).
• PD-L1 \<50% by local testing (SP 142 excluded)
• ≥70 years
• ECOG 0-2
• G8 screening score of ≤14 and/or ineligible for full-dose chemotherapy, defined as doses of carboplatin AUC 5, pemetrexed 500 mg/m2, paclitaxel 175 mg/m2, gemcitabine 1200 mg/m2 (as per Investigator)
• Life expectancy ≥6 months
• Patients with a prior malignancy (except NSCLC, see EC 7.2.2 and 7.2.3) and treated with curative intent are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence, after consultation with CI.
• Patients with asymptomatic untreated or symptomatic treated CNS metastases are eligible if corticosteroid dose \<10 mg prednisolone equivalent/day for at least 7 days
• Patients must be suitable to receive reduced-dose carboplatin-doublet chemotherapy in combination with immunotherapy including adequate bone marrow, renal and hepatic function as follows:
• Hemoglobin ≥90 g/L, neutrophils ≥1.5 G/L, Thrombocytes ≥100G/L
• Creatinine clearance (Cockroft-Gault) ≥30 mL/min
• ASAT/ALAT ≤2xULN, Bilirubin ≤1.5xULN (≤3xULN for patients with Gilbert's disease),
• Men agree not to donate sperm or father a child during trial treatment and until 6 months after the last dose of trial treatment

Exclusion criteria

• Actionable genomic alteration for 1L treatment (EGFR, ALK, ROS1, RET, NTRK, MET Exon14 skipping). Testing is required for any NSQ-NSCLC or patients with SCC and a smoking history of ≤10py.
• Prior systemic treatment for metastatic NSCLC.
• Prior chemotherapy and/or immunotherapy in curative-intent treatment for locally advanced NSCLC in the past 6 months.
• Oligometastatic treatment concept with induction systemic therapy and planned LAT to all lesions.
• High tumor burden with a risk of rapid critical progression, as judged by the Investigator. Careful patient selection is important in order to prevent that patients in the comparator arm are not eligible for receiving add-on reduced-dose chemotherapy anymore if primary progression occurs (e.g., pericardial infiltration, high liver metastasis load etc).
• Active, treatment-requiring auto-immune disease in the past 2 years other than vitiligo, alopecia, hypothyroidism, type 1 diabetes or diet-controlled celiac disease.
• History of pneumonitis in the past 5 years.
• Systemic corticosteroid treatment ≥10 mg/day of prednisolone-equivalent or any other systemic immunosuppressive medication within 7 days prior to first dose of study intervention (except as needed for chemotherapy premedication or for physiologic corticosteroid replacement)
• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
• Uncontrolled infection with HIV, hepatitis B or hepatitis C infection
• Receipt of a live vaccine within 4 weeks of start of study medication
• Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication
• Organ transplant