What are the indications for cemiplimab (Libtayo)?

Indications of Cemiplimab (Libtayo)

Cemiplimab (Libtayo) is FDA-approved for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or radiation, locally advanced or metastatic basal cell carcinoma (BCC) after hedgehog pathway inhibitor therapy, and non-small cell lung cancer (NSCLC) either as monotherapy for PD-L1 ≥50% tumors or in combination with platinum-based chemotherapy regardless of PD-L1 status. 1

Approved Indications in Detail

Cutaneous Squamous Cell Carcinoma (CSCC)

• Treatment of patients with metastatic CSCC (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation 1
• First FDA-approved treatment specifically for advanced CSCC 2
• Demonstrated durable responses with an acceptable safety profile in phase II EMPOWER-CSCC 1 trial 3

Basal Cell Carcinoma (BCC)

• Treatment of patients with locally advanced or metastatic BCC (laBCC or mBCC) who have:
  • Been previously treated with a hedgehog pathway inhibitor, OR
  • For whom a hedgehog pathway inhibitor is not appropriate 1
• Showed meaningful antitumor activity with 22% objective response rate in patients who progressed on or were intolerant to hedgehog pathway inhibitors 4

Non-Small Cell Lung Cancer (NSCLC)

1. As monotherapy:

   • First-line treatment of adult patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥50%) as determined by an FDA-approved test
   • For patients with no EGFR, ALK, or ROS1 aberrations
   • For locally advanced disease where patients are not candidates for surgical resection or definitive chemoradiation, or for metastatic disease 1, 5

2. In combination with platinum-based chemotherapy:

   • First-line treatment of adult patients with NSCLC with no EGFR, ALK, or ROS1 aberrations
   • For locally advanced disease where patients are not candidates for surgical resection or definitive chemoradiation, or for metastatic disease 1, 5

NSCLC Treatment Recommendations by PD-L1 Status

PD-L1 TPS ≥50%

• Cemiplimab monotherapy is a recommended first-line option with strong evidence (Category 1, Strong recommendation) 5
• Alternative: Cemiplimab + carboplatin + pemetrexed (for non-squamous) or cemiplimab + carboplatin + paclitaxel (for squamous) 5

PD-L1 TPS 1-49%

• Cemiplimab + carboplatin + pemetrexed (for non-squamous) or cemiplimab + carboplatin + paclitaxel (for squamous) is recommended (Strong recommendation) 5

PD-L1 TPS <1% or Unknown

• Cemiplimab + carboplatin + pemetrexed (for non-squamous) or cemiplimab + carboplatin + paclitaxel (for squamous) is recommended 5

Evidence Supporting NSCLC Indications

PD-L1 ≥50% (Monotherapy)

• Based on EMPOWER-Lung 1 trial showing median OS of 26.1 months (95% CI, 22.1 to 31.8) with HR vs chemotherapy of 0.57 (95% CI, 0.46 to 0.71) 5
• Benefit observed across both squamous (HR 0.51) and non-squamous (HR 0.64) histologies 5

Combination with Chemotherapy

• Based on EMPOWER-Lung 3 trial showing improved survival across all PD-L1 expression levels 5
• In squamous histology, median OS was 21.9 months with cemiplimab plus chemotherapy versus 13.8 months with chemotherapy alone (HR 0.56) 5

Emerging/Investigational Uses

• Being investigated for cervical cancer based on the EMPOWER-Cervical 1 trial showing improved OS, PFS, and ORR compared to chemotherapy 6
• Potential application in other HPV-related cancers including penile and vulvar SCC based on molecular similarities to cervical SCC 6
• Used as neoadjuvant therapy in resectable hepatocellular carcinoma, showing tumor necrosis in 20% of treated patients 5

Common Adverse Events

• As monotherapy: fatigue, musculoskeletal pain, rash, diarrhea, and anemia 1
• In combination with platinum-based chemotherapy: alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite 1
• Immune-mediated adverse reactions can occur in any organ system and may require corticosteroids and treatment interruption or discontinuation 1

Important Considerations

• Treatment duration for CSCC and BCC: 350 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months 1
• Treatment duration for NSCLC: 350 mg every 3 weeks until disease progression or unacceptable toxicity 1
• PD-L1 testing is required for monotherapy use in NSCLC 1
• Contraindicated in patients with history of severe immune-mediated adverse reactions to PD-1/PD-L1 inhibitors 1

Cemiplimab represents a significant therapeutic advance, particularly for CSCC where it was the first approved treatment, and continues to demonstrate efficacy across multiple tumor types with an acceptable safety profile.