Confidential data was leaked, and there was also a significant sell-off in stock prices.

But amidst the chaos surrounding Moderna and Merck's latest personalized cancer vaccine data, oncologists see something else: an important milestone in the treatment of melanoma.

On Thursday, two companies announced the detailed results of the phase three trials of this vaccine based on mRNA. Earlier on the same day, some of the data had already been leaked on social media platforms.

When this vaccine, named intismeran autogene, is used in combination with Merck's immunotherapy Keytruda, it can reduce the risk of melanoma recurrence or death by 42% compared to using Keytruda alone. According to this trial involving approximately 1,100 patients who had their tumors surgically removed, this combined regimen can also reduce the risk of cancer spreading to distant parts of the body or death by 38%, whereas the control group only received immunotherapy.

The reaction of the stock market contrasts with the judgment of six melanoma experts. The latter stated regarding CNBC, that these results represent clinically significant progress and may in the future become the standard treatment regimen for a group of patients: those who undergo surgery first and have not received immunotherapy before the operation.

Inova Schar Cancer An expert in melanoma and the principal investigator at one of the trial sites in the United States, Dr. Sekwon Jang, stated: "This could become a major breakthrough in the treatment of melanoma and even in the field of cancer immunotherapy as a whole, bringing better treatment outcomes for patients."

Dr. Janice Mehnert, an expert in skin cancer at NYU Langone Medical Center and a researcher on this trial, added, "This is the first time we have seen that adding another therapy on top of immunotherapy actually enhances its effectiveness."

It may not be long before this vaccine is available for use in melanoma patients for the first time. The CEO of Moderna, St é phane Bancel, stated in an interview before the results were announced that the company was completing the application materials to be submitted to regulatory authorities, with the goal of obtaining full approval for the drug next year.

He said, "This is a very, very joyful moment for the entire field and for the patients."

Major Advances in Melanoma Treatment

Immunotherapies like Keytruda aim to awaken the immune system to recognize and attack cancer cells. Unlike preventive vaccines, which are designed to prevent potentially carcinogenic infections, Moderna and Merck’s therapeutic vaccine are more like a “blueprint” that trains the immune system to identify and pursue residual cancer cells based on the specific mutations in each patient’s tumor.

Doctors indicate that the importance of these phase III data is not just in delaying recurrence. Once melanoma recurs after surgery and spreads to distant sites such as the lungs, brain, or liver, the difficulty of treatment significantly increases. Patients in the advanced stages may require additional treatments, including immunotherapy, radiotherapy, or further surgery, but these methods do not guarantee effectiveness.

If it is possible to prevent the recurrence of cancer, patients may be able to completely avoid the risks and complexities associated with metastatic diseases.

The director of the melanoma service at the Sloan Kettering Cancer Center and a researcher in this trial, Dr. Michael Postow, stated: "It would be a remarkable advancement if we could effectively cure more patients with early-stage melanoma and never have to deal with inoperable metastatic diseases again."

Postow indicates to CNBC that, ideally, in the future, patients may receive this vaccine and Keytruda treatment after surgery, without the need for further melanoma treatment.

However, there are still some questions that need to be answered, including whether this combined approach will ultimately help patients live longer, what the benefits are over the long-term follow-up period, and which patients will benefit the most.

Some experts also stated that these results do not fully indicate the position that this individualized vaccine will occupy in the constantly evolving landscape of melanoma treatment.

This trial tested the combination of postoperative use of Keytruda with a vaccine, rather than comparing it with the immunotherapy regimen used before surgery. For patients with melanoma who are suitable for treatment and have resectable primary tumors, preoperative immunotherapy is becoming increasingly common. The existing data do not indicate whether the vaccine regimen is more effective or less effective compared to those who received immunotherapy before surgery.

As Moderna and Merck announced detailed results at the European Society of Medical Oncology conference on Saturday, the medical community will receive more clear information.

Divergent views between investors and doctors

After some trial data was leaked on social media, the stock price of Moderna fell by 25% on Thursday, before subsequently recovering some of that loss. Although the overall results were positive, this round of selling highlighted the gap between the clinical prospects of the therapy and investors' expectations for its commercial potential. Driven by optimism regarding cancer vaccines, the stock price of Moderna has also risen by nearly 600% this year, which also increases the possibility of disappointment on Wall Street.

Analyst Trung Huynh wrote in a report on Thursday that investors had hoped that combining the vaccine with Keytruda would replicate the results of an earlier phase two trial; that trial showed a reduction in the risk of recurrence or death over a five-year period of about 49%. Huynh described the phase three results as clinically significant and possibly sufficient to support regulatory approval, but he noted that the main efficacy results fell at the lower end of the investors' expectations.

However, there is a key difference between the two studies. Dr. George Ansstas, who heads the melanoma department at Washington University in St. Louis, stated that the phase three trials included a wider range of patients with varying risk profiles, including some who had a lower risk of recurrence than those enrolled in the earlier phase two trials. This may have somewhat lowered the overall results, as patients with lower risk inherently have a lower probability of recurrence to begin with.

Ansstas also participated in the second-phase trial. He said, 'In fact, this is very good data. Overall, it is consistent with the results we demonstrated in the second-phase trial.'

Both companies stated that in the first 6 months of treatment, there was not much difference between the combined regimen and using Keytruda alone. However, another analysis of the phase three data provided more encouraging results: after 6 months, the combination of the vaccine and Keytruda reduced the risk of recurrence or death by 58% compared to using Keytruda alone.

Ansstas indicates that the benefits of personalized cancer vaccines may not become apparent until several months later, as each dose must be custom-produced, a process that takes about 6 weeks. During this time, patients will begin receiving Keytruda treatment first. After vaccination begins, it also takes time and repeated dosing for the immune system to develop a response against the tumor.

Ansstas says that this timeline may explain why patients who accepted the combined treatment saw greater benefits after about 6 months. However, this explanation remains a hypothesis and is not evidence regarding when the vaccine began to take effect.

Experts in melanoma at the University of Texas MD Anderson Cancer Center and trial researcher, Dr. Hussein Tawbi, also emphasized that the side effects associated with this vaccine are relatively mild, including reactions at the injection site.

Keytruda and other cancer therapies may cause potentially serious immune-related side effects. The detailed safety results announced on Saturday should help to clarify the trade-offs of incorporating vaccines into immunotherapy regimens more clearly.

There is still more work to be done.

For Moderna, the stakes are not just melanoma. The company is working hard to build its business beyond COVID-19 vaccines, while Merck is preparing for Keytruda to eventually lose its patent protection.

There are still several obstacles ahead for both companies, including how to sell on a large scale an individualized therapy that requires several weeks of customization for each patient.

The co-director of the Melanoma Center at the University of California, San Francisco, and the lead researcher of the phase three trial, Dr. Adil Daud, stated: "I think the downside is that it is very labor-intensive, and you have to produce vaccines for each individual separately. Therefore, you can't simply stockpile one million vaccines and then deliver them whenever someone needs them. There are issues related to time and cost involved, and the expenses are likely to be very high."

Moderna and Merck have not yet disclosed the production cost details of this vaccine.

Daud also indicates that most patients who come to the clinic with tumors that have not yet been surgically removed may still choose to receive Keytruda before surgery, because "this method is simpler and does not cause patients to have to wait for the delay in vaccine preparation."

Daud said that he expects this combined vaccine approach to be mainly used in adjuvant therapy scenarios, that is, after surgery, rather than replacing the existing pre-surgical immunotherapy regimens. He stated that for those patients who receive immunotherapy before surgery but have a minimal response or no response at all, this combined approach may provide another option, although it is likely to be applicable only to a smaller portion of patients.

Daud indicates that for many other patients, doctors may still insist on providing treatment before surgery, including the use of Keytruda alone or in combination with multiple immunotherapies.

Moderna and Merck still need to verify this method in other types of cancer, including non-small cell lung cancer, bladder cancer, and renal cell cancer. Success with melanoma does not automatically mean that this method will also be effective in other tumors.

Before the results were announced, Dean Li, President of Merck Research Laboratories, said in an interview: "I can dream of building a wooden house, but right now we only have some wood, and we just cut down a tree. Cutting down a tree doesn't mean you suddenly have a wooden house or a village."

The Bancel of Moderna is optimistic about the future of this vaccine. He stated that he believes it will ultimately be able to help “tens of thousands, even hundreds of thousands, or perhaps even millions of people with different types of tumors around the world.”