Detailed Phase 3 data for Moderna and Merck’s personalized mRNA cancer vaccine, intismeran autogene, reveal a 42% reduction in melanoma recurrence or death when combined with Keytruda, following an unexpected data leak ahead of the European Society for Medical Oncology conference in Madrid.
The leak disrupted proceedings on the eve of the European Society for Medical Oncology conference, statnews.com reported, forcing the co-developers to release comprehensive trial findings early. Despite the market volatility and a subsequent stock sell-off noted by CNBC, oncologists evaluating the roughly 1,100-patient trial data characterized the results as a clinically meaningful advancement for resectable melanoma.
Custom mRNA Vaccine Trains Immune System to Fight Cancer
- Personalized Blueprint: Unlike preventative vaccines, which protect against infections that can cause cancer, this mRNA shot is custom-built based on the specific mutations in an individual patient’s tumor.
- Immune Activation: The vaccine acts as a blueprint to train the immune system to recognize and hunt residual cancer cells left behind after surgery.
- Measurable Risk Reduction: Clinical trials demonstrated that combining the vaccine with the immunotherapy drug Keytruda significantly lowered the likelihood of the cancer returning compared to immunotherapy alone.
Combination Therapy Reduces Melanoma Recurrence Risk by 42%
In the trial evaluating patients whose tumors were surgically removed, the primary endpoint assessed recurrence-free survival. At 24 months, the recurrence-free survival rate reached 82.2% in the combination cohort compared to 70.0% in the Keytruda control arm, yielding a hazard ratio of 0.58, according to fiercebiotech.com. This difference confirms a 42% reduction in the risk of melanoma recurrence or death.
Regarding secondary endpoints, the trial tracked distant metastasis-free survival to determine how effectively the combination prevented cancer from spreading to distant parts of the body, such as the lungs, liver, or brain. At 24 months, the distant metastasis-free survival rate was 88.5% for the vaccine combination versus 80.2% for the control arm, reflecting a hazard ratio of 0.62 or a 38% risk reduction, as reported by fiercebiotech.com. While analysts noted this metric fell short of expectations set by the phase 2 readout, clinical investigators emphasized that an absolute reduction of approximately 10% in the risk of developing metastases is quite compelling for patient outcomes.
Oncologist Perspectives and Regulatory Timelines
“If we can essentially cure more patients with earlier-stage melanoma and never have to deal with unresectable metastatic disease — that’s a wonderful advance,” Dr. Michael Postow, who serves as an investigator on the study and leads the Melanoma Service at Memorial Sloan Kettering Cancer Center, shared with CNBC. Dr. Janice Mehnert, trial investigator and skin cancer expert at NYU Langone, further commented that the study demonstrates for the first time that adding an agent to immunotherapy can actually enhance the effectiveness of the immunotherapy.
Moderna CEO Stéphane Bancel stated that the company is finishing a filing with regulators with the goal of getting the drug fully approved next year, moving the individualized mRNA therapeutic closer to standard clinical practice.
Combination Therapy Increases Risk of Adverse Events
Treatment-related adverse events occurred in 95.8% of patients receiving the vaccine combination compared to 90% in the control arm, with grade 3 to 5 events reported in 14.2% of combination therapy participants.
References
- European Society for Medical Oncology Conference Data.
- Clinical Trial Findings: Intismeran Autogene and Keytruda in Resectable Melanoma (Phase 3 Trial Data via CNBC and FierceBiotech).
- Memorial Sloan Kettering Cancer Center Melanoma Service Clinical Evaluations.
