Merck's Keytruda Shows 42% Reduction in Distant Metastasis in Phase 3 Merkel Cell Carcinoma Adjuvant Therapy, But Fails to Achieve RFS Goal
Background and Data on the Failure to Achieve the Primary Endpoint in the Phase 3 Trial
The STAMP Phase 3 (EA6174) trial evaluated Merck & Co.'s (MRK) PD-1 immune checkpoint inhibitor, Keytruda (pembrolizumab), as an adjuvant therapy compared to observation in 293 patients with Stage 1-3 Merkel Cell Carcinoma (MCC) following surgery. The 2-year Relapse-Free Survival (RFS) rate was 73% in the Keytruda group and 66% in the observation group, resulting in a 20% reduction in the risk of recurrence, but this did not reach statistical significance (HR 0.80, p=0.105). Merkel Cell Carcinoma is an aggressive cancer with an extremely high rate of local recurrence, and this result reflects the inherent difficulty in preventing all recurrences with surgery alone. However, it may serve as an important milestone in that it presents a new clinical possibility for patients in the early stages, where treatment options are extremely limited.
Clinical Significance of Distant Metastasis Inhibition and Secondary Endpoint
Although the primary endpoint did not reach statistical significance, Keytruda demonstrated encouraging therapeutic efficacy in secondary endpoints. In particular, in the Distant Metastasis-Free Survival (DMFS) endpoint, which measures the prevention of systemic spread of cancer cells, Keytruda significantly reduced the risk of distant metastasis by 42% compared to the observation group (HR 0.58, p=0.032). Furthermore, additional analysis presented at the 2026 ASCO Annual Meeting showed that the Merkel Cell Carcinoma-specific Relapse-Free Survival (RFS_b) was also 77% in the Keytruda group and 67% in the observation group at 2 years, demonstrating statistical significance (HR 0.66, p=0.032). This suggests that, even if it does not prevent local recurrence, delaying distant metastasis, which has a decisive impact on patient survival, can lead to tangible survival benefits.
Unmet Needs in the Merkel Cell Carcinoma Treatment Market and Competitive Landscape
The global Merkel Cell Carcinoma treatment market is a high-growth, high-value rare cancer market, expected to grow from $3.77 billion in 2025 to $7.21 billion by 2035. In the metastatic market, Pfizer (PFE) with Bavencio (avelumab), approved in March 2017, and Incyte (INCY) with Zynyz (retifanlimab), approved in March 2023, are competing. Keytruda received FDA accelerated approval in December 2018 for the treatment of metastatic patients, but the adjuvant therapy setting after surgery still has unmet needs, with patients relying solely on observation. This Phase 3 data, while not meeting the criteria for approval, provides clinical evidence for personalized treatment for high-risk patients.
Prospects for Future Regulatory Procedures and Diversification of the Adjuvant Therapy Market
This trial was an investigator-initiated trial (IIT) led by ECOG-ACRIN, supported by the U.S. National Cancer Institute (NCI), and there are no separate commercial license fees. Due to the failure to meet the primary endpoint, it is expected that Merck will not be able to obtain immediate FDA approval for Keytruda as an adjuvant therapy. However, given the significant effects on distant metastasis inhibition (DMFS) and disease-specific benefits (RFS_b), it is possible that it will be listed in the NCCN guidelines as a recommended treatment for high-risk patients. This is expected to indirectly help Merck defend its market share by encouraging off-label use in clinical practice even before regulatory approval.
This Phase 3 STAMP study failed to achieve statistical significance in its primary endpoint of 2-year Relapse-Free Survival (RFS) (HR 0.80, p=0.105), but demonstrated a 42% reduction in risk in the secondary endpoint of Distant Metastasis-Free Survival (DMFS) (HR 0.58, p=0.032), signaling a potential paradigm shift in the adjuvant therapy market, where treatment options have been lacking. In the global Merkel Cell Carcinoma (MCC) market, which is projected to grow from $3.77 billion in 2025 to $7.21 billion in 2035, Merck (MRK) is seeking to proactively enter the adjuvant therapy market after surgery with Keytruda, while Pfizer (PFE)'s Bavencio and Incyte (INCY)'s Zynyz dominate the metastatic disease area. From the perspective of researchers and industry experts, future research on combination therapies, such as radiation therapy, is expected to be further accelerated to overcome the characteristics of Merkel Cell Carcinoma, which has a very high rate of local recurrence. From an investor perspective, even if immediate FDA approval is delayed, the listing in the NCCN guidelines and the activation of off-label use will be key variables in Merck's medium- to long-term market share defense and dominance.
Source: ClinicalTrials.gov (api_ct)