Adjuvant CSCC Rivalry: Why Libtayo's ASCO25 Triumph Positions Regeneron to Dominate the Immuno-Oncology Landscape

The adjuvant treatment of high-risk cutaneous squamous cell carcinoma (CSCC) is undergoing a seismic shift, thanks to Regeneron's Libtayo (cemiplimab). At the 2025 American Society of Clinical Oncology (ASCO) conference, data from the pivotal Phase 3 C-POST trial cemented Libtayo's status as the first systemic therapy to demonstrate statistically significant disease-free survival (DFS) benefits in this indication. Meanwhile, Merck's Keytruda (pembrolizumab)—the PD-1 market giant—remains relegated to the shadows, with no direct adjuvant CSCC data presented and an implicit failure noted in a competing trial. This article dissects how Libtayo's clinical differentiation could carve out a multi-billion-dollar niche, while Keytruda's absence in this critical space signals a missed opportunity for Merck.

The Clinical Divide: Libtayo's Data Dominates Adjuvant CSCC

The C-POST trial's headline result—a 68% reduction in disease recurrence or death (HR 0.32, p<0.0001)—is a game-changer. At two years, 87% of Libtayo-treated patients remained recurrence-free versus 64% on placebo. This stark contrast is amplified by the drug's ability to reduce both local/regional recurrence (80% risk reduction) and distant metastasis (65% reduction). The trial's publication in the New England Journal of Medicine and simultaneous regulatory submissions to the FDA and EMA underscore its clinical and commercial maturity.

Keytruda, by contrast, has no comparable data in adjuvant CSCC. While the ASCO abstracts noted “negative results with another PD-1 inhibitor,” Merck has not disclosed whether this refers to its own trials. Even in adjacent head and neck squamous cell carcinoma (HNSCC), where Keytruda's adjuvant data (KEYNOTE-689) showed promise, the drug's impact in CSCC remains unproven. This lack of direct evidence leaves Libtayo as the sole PD-1 with a validated role in adjuvant CSCC, a distinction that could define market share.

Safety Profile: A Balanced Risk-Benefit Equation

Libtayo's safety data reveal a trade-off familiar in immunotherapy: higher efficacy comes with more immune-related adverse events (AEs). Grade ≥3 AEs occurred in 24% of Libtayo patients vs. 14% on placebo, though serious AEs leading to discontinuation were manageable (10% vs. 2%). This profile mirrors Keytruda's established safety in other indications, suggesting no inherent class advantage. However, Libtayo's DFS superiority likely outweighs minor AE differences in risk-benefit analyses.

Merck's silence on adjuvant CSCC safety further disadvantages Keytruda. Without head-to-head data, clinicians will default to the drug with proven efficacy—a clear win for Regeneron.

Market Capture: A $2B+ Niche Awaits the First-Mover

Adjuvant CSCC represents a high-value, underpenetrated market. With an estimated 1.2 million global cases annually, only a fraction of high-risk patients (e.g., those with positive margins or perineural invasion) qualify for adjuvant therapy. However, Libtayo's DFS data position it as the new standard of care post-surgery, potentially capturing $2 billion in annual sales by 2030.

Merck's Keytruda, despite its PD-1 dominance in metastatic CSCC and other cancers, lacks the adjuvant CSCC data needed to compete here. Its reliance on neoadjuvant trials (e.g., the De-Squamate study) focuses on avoiding surgery—a niche approach—while Libtayo tackles the larger post-surgical population. This strategic misalignment could cost Merck billions as oncologists prioritize Libtayo for DFS benefits.

Investment Implications: Regeneron's Surge vs. Merck's Stall

The stock market has already begun pricing in this divergence. Regeneron's shares have surged +18% YTD, while Merck's PD-1-driven growth has slowed to +3% amid biosimilar pressures. The FDA's impending decision on Libtayo's adjuvant CSCC application (expected Q3 2025) could accelerate this trend, with analysts predicting a 25% earnings boost for Regeneron.

For investors, the calculus is clear:
- Regeneron: Buy the innovator with a first-in-class indication and a regulatory tailwind.
- Merck: Avoid reliance on PD-1's legacy markets as competitors encroach.

Conclusion: The Adjuvant CSCC Race Is Over—Libtayo Won

ASCO2025's data confirm Libtayo's ascendancy in adjuvant CSCC, a position Keytruda cannot contest without its own trial results. Regeneron's early leadership in this $2B+ niche positions it to dominate immuno-oncology's next frontier, while Merck's silence underscores a strategic misstep. Investors seeking exposure to transformative oncology therapies should pivot to Regeneron now—before the market fully discounts this breakthrough.

The clock is ticking. Act before the FDA's decision makes this opportunity price-in.

Note: Clinical data sourced from ASCO2025 abstracts and regulatory filings. Market estimates derived from EvaluatePharma and internal analyses.