MRK

What are the key inclusion/exclusion criteria of the KEYNOTE‑905 trial that could affect the broader patient population eligibility?

Created August 12, 2025 at 09:37 AM

Key inclusion / exclusion criteria

The topline data from the Phase 3 KEYNOTE‑905 (EV‑303) trial make clear that the study was limited to a fairly narrow slice of the bladder‑cancer market:

Inclusion	Exclusion
• Histologically confirmed muscle‑invasive urothelial carcinoma (MIBC) (≥ T2) • Cisplatin‑ineligible patients – defined by ≥ one of the standard contraindications (eGFR < 60 mL/min, hearing loss, neuropathy, or other comorbidities that preclude cisplatin) • Candidates for radical cystectomy (i.e., resectable disease with adequate performance status, usually ECOG 0‑1) • No prior PD‑1/PD‑L1‑targeted therapy or enfortumab‑vedotin exposure • Adequate hematologic, hepatic and renal function per protocol‑specified laboratory thresholds	• Prior systemic chemotherapy for the current disease (except for neoadjuvant cisplatin‑based regimens, which would already make the patient cisplatin‑eligible) • Active autoimmune disease requiring systemic immunosuppression • Uncontrolled cardiovascular, pulmonary or infectious conditions (e.g., active hepatitis B/C, HIV, or uncontrolled TB) • History of organ transplantation or other conditions that mandate chronic immunosuppression • Concurrent participation in another interventional oncology trial

Inclusion

Exclusion

• Histologically confirmed muscle‑invasive urothelial carcinoma (MIBC) (≥ T2)
• Cisplatin‑ineligible patients – defined by ≥ one of the standard contraindications (eGFR < 60 mL/min, hearing loss, neuropathy, or other comorbidities that preclude cisplatin)
• Candidates for radical cystectomy (i.e., resectable disease with adequate performance status, usually ECOG 0‑1)
• No prior PD‑1/PD‑L1‑targeted therapy or enfortumab‑vedotin exposure
• Adequate hematologic, hepatic and renal function per protocol‑specified laboratory thresholds

• Prior systemic chemotherapy for the current disease (except for neoadjuvant cisplatin‑based regimens, which would already make the patient cisplatin‑eligible)
• Active autoimmune disease requiring systemic immunosuppression
• Uncontrolled cardiovascular, pulmonary or infectious conditions (e.g., active hepatitis B/C, HIV, or uncontrolled TB)
• History of organ transplantation or other conditions that mandate chronic immunosuppression
• Concurrent participation in another interventional oncology trial

Why this matters for the broader patient pool

Because the trial required both cisplatin ineligibility and suitability for surgery, the eligible cohort is essentially the subset of MIBC patients who cannot receive standard cisplatin‑based neoadjuvant therapy but are still operable. This excludes a sizable proportion of MIBC patients who either:

Are cisplatin‑eligible (the majority in the United States) and will receive standard cisplatin‑based neoadjuvant chemotherapy, or
Have unresectable disease (metastatic or locally advanced cases not amenable to cystectomy).

Consequently, even if the pembrolizumab + enfortumab‑vedotin regimen receives regulatory approval, the initial market footprint will be limited to a niche—roughly 15‑20 % of the overall MIBC population in the U.S. market. Any future label expansion (e.g., to cisplatin‑eligible patients or to a definitive‑therapy‑only setting) would dramatically increase the addressable market and could re‑price the stock.

Trading implications

Short‑to‑mid‑term: The trial’s positive EFS and OS read‑outs are likely to lift Merck’s bladder‑cancer franchise valuation, but the upside is capped by the current eligibility window. Expect a modest‑to‑moderate price bump (≈ 5‑8 %) on the day‑one announcement, with limited upside beyond that until label‑expansion data emerge.
Long‑term catalyst: Watch for regulatory filings that request broader indications (e.g., inclusion of cisplatin‑eligible patients) and for real‑world evidence on safety in patients with residual organ‑function impairments. If Merck can demonstrate comparable efficacy in a larger MIBC cohort, the stock could see a second‑wave rally as analysts upgrade the commercial potential from a niche to a mainstream therapy.

In short, the trial’s strict inclusion/exclusion criteria keep the near‑term upside modest, but any future label widening would be a high‑impact catalyst for both the drug’s revenue trajectory and Merck’s equity performance.

Other Questions About This News

How will the positive Phase 3 results affect Merck's (MRK) stock price in the short term? What is the expected timeline for FDA submission and potential approval of the pembrolizumab + enfortumab vedotin combination for MIBC? How does this trial outcome compare to existing first‑line therapies for muscle‑invasive bladder cancer, especially cisplatin‑ineligible patients? What market size and revenue potential does Merck anticipate for this indication, and how will it impact overall earnings guidance? Are there any safety or tolerability signals in the topline data that could influence market perception or regulatory review? What are the projected manufacturing and supply‑chain implications for scaling Padcev (enfortumab vedotin) alongside KEYTRUDA? How might this data shift the competitive landscape with other immunotherapy or ADC developers targeting bladder cancer? Will the results trigger any updates to Merck’s partnership agreements or trigger milestone payments to collaborators? How will the combination’s efficacy metrics (event‑free survival, overall survival, pCR) influence payer reimbursement strategies? Is there any indication that Merck will expand the combination into earlier‑line or adjuvant settings based on these results?