Confidential data has been leaked, and the stock price has experienced significant selling pressure.
But beneath the chaos surrounding the latest personalized cancer vaccine data from Moderna and Merck, oncologists are seeing something else: a significant milestone in melanoma treatment.
The two companies released the detailed Phase 3 trial results for the mRNA-based vaccine on Thursday. Earlier that day, some of the data had been leaked on social media platforms.
The vaccine, named Intismeran autogene, when used in combination with Merck’s immunotherapy Keytruda, reduced the risk of melanoma recurrence or death by 42% compared to Keytruda alone. According to a trial involving approximately 1,100 patients who had undergone surgical removal of their tumors, the combination therapy also reduced the risk of cancer spreading to distant parts of the body or death by 38%, compared to the control group that received immunotherapy alone.
The market's reaction contrasts with the assessment of six melanoma experts, who told CNBC that these results represent a clinically meaningful advancement and could potentially become the standard treatment for a specific group of patients: those who undergo surgery without prior immunotherapy.
Dr. Sekwon Jang, a melanoma specialist at Inova Schar Cancer Institute and the principal investigator for one of the U.S. trial sites, said: “This could represent a major breakthrough in melanoma treatment and the broader field of cancer immunotherapy, leading to improved outcomes for patients.”
Dr. Janice Mehnert, a skin cancer expert and trial investigator at NYU Langone Health, added, “This is the first time we’ve seen that adding another therapy to immunotherapy actually enhances the effectiveness of immunotherapy.”
The vaccine may be close to entering the market for melanoma patients. Before the results were announced, Moderna’s CEO Stéphane Bancel said the company is finalizing its submission to regulators with the goal of obtaining full approval for the drug next year.
He said, "This is an incredibly exciting moment for the entire field and for patients."
Major advances in melanoma treatment
Immunotherapies like Keytruda work by activating the immune system to recognize and attack cancer cells. Unlike preventive vaccines, which aim to prevent infections that may lead to cancer, Moderna and Merck’s therapeutic vaccine acts more like a “blueprint,” training the immune system to identify and hunt down residual cancer cells based on specific mutations in each patient’s tumor.
Doctors stated that the importance of this Phase III data goes beyond delaying recurrence. Once melanoma recurs after surgery and spreads to distant sites such as the lungs, brain, or liver, treatment becomes significantly more challenging. Patients with advanced disease may require additional therapies, including immunotherapy, radiation, or further surgery—but these approaches do not guarantee effectiveness.
If cancer recurrence can be prevented, patients may completely avoid the risks and complexities associated with metastatic disease.
Dr. Michael Postow, head of the Melanoma Service at Memorial Sloan Kettering Cancer Center and an investigator of the trial, said: “It would be an extraordinary advancement if we could essentially cure more patients with early-stage melanoma and never have to confront unresectable metastatic disease.”
Postow told CNBC that, ideally, future patients might receive this vaccine and Keytruda after surgery, without needing further melanoma treatment.
However, some questions remain unanswered, including whether this combined approach will ultimately help patients live longer, what the long-term benefits are with extended follow-up, and which patients benefit the most.
Some experts also noted that these results do not fully clarify where this personalized vaccine will stand in the evolving landscape of melanoma treatment.
This trial tests the vaccine in combination with Keytruda after surgery, rather than comparing it to preoperative immunotherapy regimens. Preoperative immunotherapy is becoming increasingly common for melanoma patients who are eligible for treatment and have resectable primary tumors. Existing data do not show whether the vaccine regimen is superior or inferior to preoperative immunotherapy.
The medical community will gain more clarity as Moderna and Merck release detailed results at the European Society for Medical Oncology conference on Saturday.
Investors and doctors hold differing views
After partial data from the trial leaked on social media, Moderna's stock dropped as much as 25% on Thursday before recovering some of those losses. Despite overall positive results, this sell-off highlights the gap between the therapy’s clinical prospects and investors’ expectations for its commercial potential. Driven by optimism around the cancer vaccine, Moderna’s stock has already risen nearly 600% this year, increasing the likelihood of disappointment on Wall Street.
RBC Capital Markets analyst Trung Huynh wrote in a report on Thursday that investors had hoped the vaccine, when used in combination with Keytruda, would replicate the results of an earlier Phase II trial, which showed approximately a 49% reduction in the risk of recurrence or death over five years. Huynh described the Phase III results as clinically meaningful and potentially sufficient to support regulatory approval, but noted that the primary efficacy outcome fell at the lower end of investor expectations.
However, there is a key difference between the two studies. Dr. George Ansstas, head of the Melanoma Division at Washington University in St. Louis, noted that the Phase III trial included a broader spectrum of patients, including some with a lower risk of recurrence than those enrolled in the earlier Phase II trial. This may have somewhat lowered the results, as low-risk patients inherently have a lower likelihood of recurrence.
Ansstas also participated in the Phase II trial. He said, "These are actually very good data, consistent overall with the results we demonstrated in the Phase II trial."
Both companies stated that, during the first six months of treatment, the combination regimen showed little difference compared to Keytruda alone. However, another analysis of the Phase III data provided a more encouraging signal: after six months, the vaccine plus Keytruda reduced the risk of recurrence or death by 58% compared to Keytruda alone.
Anstas said that the benefits of personalized cancer vaccines may take several months to become apparent, as each dose must be custom-produced—a process that takes about six weeks—during which patients will begin receiving Keytruda. After vaccination begins, the immune system also requires time and repeated dosing to develop a response against the tumor.
Anstas said this timeline may help explain why patients who received the combined regimen saw greater benefits at around six months. However, this explanation remains hypothetical and is not evidence of when the vaccine begins to take effect.
Dr. Hussein Tawbi, a melanoma expert and trial investigator at MD Anderson Cancer Center at the University of Texas, also emphasized that the side effects associated with this vaccine are relatively mild, including injection-site reactions.
Keytruda and other cancer therapies may trigger potentially serious immune-related side effects. The detailed safety results released on Saturday should help clarify the trade-offs of adding a vaccine to immunotherapy regimens.
There is still more work to be done.
For Moderna, the stakes extend beyond melanoma. The company is working to build a business beyond its COVID-19 vaccine, while Merck is preparing for the eventual loss of patent protection for Keytruda.
The two companies still face several challenges ahead, including how to scale the sale of a personalized therapy that takes weeks to manufacture for each individual patient.
Dr. Adil Daud, Co-Director of the Melanoma Center at the University of California, San Francisco, and lead investigator of the Phase 3 trial, said: “I think the downside is that it is very labor-intensive, and you have to manufacture a vaccine individually for each person, so you can’t simply stockpile one million doses and ship them out when needed. There are time and cost implications, and the cost is likely to be very high.”
Moderna and Merck have not disclosed details regarding the production cost of this vaccine.
Daud also noted that most patients who visit the clinic with tumors that have not yet been surgically removed may still opt to receive Keytruda before surgery, because "this approach is simpler and avoids the delay associated with waiting for vaccine preparation."
Daud said he expects this combination vaccine approach to be primarily used in an adjuvant setting, such as after surgery, rather than replacing existing preoperative immunotherapy regimens. He noted that for patients who received preoperative immunotherapy but had little or no response, this combination could offer an alternative option, though it would likely apply to only a small subset of patients.
Daud said that for many other patients, doctors may still insist on providing treatment before surgery, including Keytruda alone or in combination with multiple immunotherapies.
Moderna and Merck still need to validate this approach in other cancer types, including non-small cell lung cancer, bladder cancer, and renal cell carcinoma. Success in melanoma does not automatically mean this method will work in other tumors.
Before the results were announced, Merck Research Laboratories President Dean Li said in an interview: “I can dream of building a log cabin, but right now we just have some logs, and we’ve just cut down one tree. Cutting down one tree doesn’t give you a cabin or a village.”
Bancel of Moderna is optimistic about the vaccine's future, stating that he believes it will ultimately help hundreds of thousands, even millions, of people across a wide range of tumor types worldwide.