Phase 2 cemiplimab PD-1 inhibitor plus platinum doublet chemo as neoadjuvant therapy in stage I NSCLC.

This Medical University of South Carolina (MUSC) investigator-initiated Phase 2 study tests whether adding cemiplimab (Libtayo; Regeneron Pharmaceuticals + Sanofi), a PD-1 (CD279)–blocking monoclonal antibody that reactivates antitumor T-cell activity, to platinum-doublet chemotherapy can deepen pathologic responses before surgery in clinical stage I, 2.0–3.9 cm, resectable NSCLC. Patients receive 3 cycles of cemiplimab plus investigator’s-choice platinum chemotherapy (carboplatin or cisplatin, DNA crosslinking agents) combined with pemetrexed (antifolate; for nonsquamous) or paclitaxel (microtubule inhibitor; commonly used for squamous), followed by definitive resection and postoperative safety assessments with longer-term follow-up. The key scientific angle is moving PD-1–based chemoimmunotherapy “downstage” into smaller, node-negative tumors where surgery alone is often used despite meaningful relapse risk; today’s care for most stage I NSCLC is surgery (or SBRT if inoperable) with adjuvant systemic therapy typically reserved for higher-risk features, and this explores whether short-course neoadjuvant chemoimmunotherapy can increase pathologic complete response rates in sub-4 cm disease.