Merck & Co. and Moderna have shared highly anticipated phase 3 data on their cancer vaccine, revealing a primary endpoint hit that approached analysts’ best-case scenario. But the positive result was offset by weaker-than-expected data on a key secondary endpoint.
In August, the partners revealed that the INTerpath-001 melanoma trial hit its primary endpoint, igniting a rally in their share prices and enthusiasm for cancer vaccines. However, the readout lacked the numbers behind the primary endpoint hit, leaving unanswered questions about the results. The detailed data, shared Thursday ahead of the European Society for Medical Oncology (ESMO) Congress 2026, answer those questions.
The data had originally been slated for release during a Saturday ESMO presentation, but that schedule moved up Thursday after the results were leaked. An ESMO press representative confirmed to Fierce that there had been an embargo breach, which occurred when an oncology news website posted some of the data ahead of its scheduled release, according to Stat.
The companies also took it upon themselves to share the results in the wake of the embargo blunder.
Taking a closer look at the data, the primary endpoint in the trial assessed recurrence-free survival (RFS) among patients receiving intismeran autogene and Keytruda compared with Keytruda alone. At 24 months, the RFS rate in the cancer vaccine combination cohort was 82.2%, versus 70.0% in the Keytruda control cohort. The hazard ratio was 0.58, indicating that adding the investigational cancer vaccine to Keytruda reduced the risk of recurrence or death by 42%.
Based on phase 2 data, analysts and key opinion leaders had predicted the hazard ratio could be as low as 0.5. However, as TD Cowen analysts observed in an Aug. 19 note to investors, Moderna executives have emphasized that outcomes ranging from 0.5 to 0.8 could be meaningful depending on the overall data package. A physician cited the same range in a Guggenheim Securities note published Aug. 21.
Hitting the low end of the range would be ideal, but “commercial enthusiasm” will rest on the totality of the evidence, TD Cowen analysts said. Similarly, William Blair analysts, writing in an Aug. 19 note, said there was some leeway for hazard ratios above 0.5 to be acceptable.
While the RFS result is in line with expectations, the data on distant metastasis-free survival (DMFS) fell short of expectations set by the phase 2 readout. At 24 months, the DMFS rate in the cancer vaccine cohort was 88.5%, compared with 80.2% in the Keytruda control arm. The hazard ratio was 0.62, indicating a 38% reduction in the risk of distant metastasis or death.
Merck and Moderna reported a 65% reduction in the risk of distant metastasis or death in the primary analysis of the phase 2 trial. The DMFS risk reduction in the five-year analysis of the phase 2 trial was 59%.
DMFS is “more interesting” than RFS because “it relates to metastatic disease and mortality,” the physician told Guggenheim. Moderna executives have “consistently highlighted DMFS as a particularly meaningful endpoint in melanoma, noting that distant metastatic recurrence is associated with worse outcomes, more intensive treatment and increased mortality risk,” TD Cowen analysts said.
Oncologists generally make treatment decisions based on absolute benefit rather than hazard ratios, the physician told Guggenheim. Most oncologists would regard “an absolute reduction of approximately 10% in the risk of developing metastases as quite compelling,” the physician said.
Going into the phase 3 readout, analysts and experts named safety and tolerability as areas where the cancer vaccine could have an edge over the existing neoadjuvant combination of CTLA-4 and PD-1 blockade. In the phase 3 trial, treatment-related adverse events occurred in 95.8% of patients receiving the cancer vaccine combination, compared with 90% in the Keytruda control arm. Grade 3 to 5 treatment-related adverse events occurred in 14.2% and 13.4% of patients, respectively. Merck and Moderna said no new safety signals were observed.
Merck and Moderna's detailed cancer vaccine data drop was arguably the biggest event of this year's ESMO meeting in Madrid, with the leak potentially taking some of the wind out of the partners' sails.
Following the unexpected release of the results Thursday afternoon, shares in both companies fell, with Merck down modestly and Moderna seeing a considerably sharper decline.
In addressing the leak, ESMO's press office told Fierce that the full dataset on intismeran autogene had been released, though Merck and Moderna's presentation will go ahead as planned Saturday.