Merck & Co. and Moderna always knew they would be making headlines in Madrid this week—just not in the way it panned out.
The partners’ detailed data for a phase 3 win of their cancer vaccine intismeran autogene was set to be the highlight of the European Society for Medical Oncology (ESMO) Congress, given the honor of the coveted Presidential Symposium on Saturday.
But an unexpected leak of the ESMO data on Thursday forced the partners to rework their plans and go public with their findings two days early. Amid the drama, the share price of both companies took a hit as investors scrambled to digest the data.
Those data showed that at 24 months, patients receiving intismeran and Merck's megablockbuster oncology therapy Keytruda saw a recurrence-free survival (RFS) rate of 82.2%, compared to 70% for patients receiving Keytruda alone in certain patients with melanoma. The hazard ratio was 0.58, indicating that adding the investigational cancer vaccine to Keytruda reduced the risk of recurrence or death by 42% in the deadliest form of skin cancer.
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.
In an interview on the ESMO sidelines on Saturday morning, Shweta Jain, vice president of global clinical development and oncology clinical research at Merck, acknowledged that the phase 2 results had amped up expectations for the phase 3 readout.
“People should have expectations; I don't think we can change that,” Jain told Fierce.
“I think hype or no hype, the question is: what did you do for the patients?” she continued. “To us, when you look at the totality of package, it does seem the benefit is real. It seems like we are edging towards that curative potential. So we are confident and we remain happy with the data.”
Jain singled out the intismeran-Keytruda combo's potential to reduce the risk of distant metastasis or death by 38% compared to Keytruda alone as “quite significant.” Distant metastasis is when cancer cells break away from the primary tumor and form new tumors in other organs.
“With this kind of powerful regimen, if you are able to decrease not only local but also distant recurrence, it does matter,” she explained. “You can keep arguing about the numbers—bottom line is, it is still a significant trial.”
With Jain and her team clearly very proud of the data, was it a blow to lose control of how the data made it out into the world?
“Look, it is unfortunate, right?” she told Fierce. “We all travel this far to make sure we have a scientifically engaged exchange of information.”
“But at the end of the day, ‘it is what it is’ is what you can tell yourself,” she added. “It happened. The data are still convincing. You know, we are able to show that the phase 3 numbers are reasonable. So that's how I'm looking at it.”
So there was no frantic re-writing of Saturday's presentation at Merck and Moderna’s offices to re-frame the data in a fresh way?
“No rewriting,” said Jain. “Nothing changed at our end. We have the same presentation. We have the same things that we were going to do. Of course, you want to do it together. You want to do it on the day of. But it happens.”
For Merck, the phase 3 data is validation of a collaboration with Moderna that stretches back to 2016, when the two companies first began working together to develop a series of mRNA vaccines.
“I think collaboration-wise, this is probably the pinnacle of how two groups of scientists can come together and think beyond the box,” Jain explained.
“There was a lot of institutional knowledge with pembrolizumab. There was a lot of understanding of how the immune system works, what sort of patients appear to benefit,” she continued. “Then there is a lot of institutional knowledge from Moderna in terms how to understand the mRNA platform, how to understand the neoantigen.”
Merck is now gearing up for a hoped-for FDA approval for intismeran next year.
“We are working as fast as possible to make sure we can get things ready and send that to the agency,” Jain told Fierce.
Meanwhile, the pharma has kicked off phase 2 studies for the vaccine in a range of other cancers, including renal cell carcinoma, bladder cancer and non-small cell lung cancer.
It’s no secret that Merck has long been seeking worthy successors to King Keytruda. As Jain sees it, intismeran is part of a “diverse strategy” that draws on the pharma’s “deeper understanding of various types of malignancies.”
This portfolio is on full display at ESMO, where Merck will also be sharing phase 3 data from its TROP2-directed antibody-drug conjugate sac-TMT in trials for endometrial cancer and non-small cell lung cancer, as well as Keytruda as a first-line treatment for a type of endometrial cancer.
“I wouldn't say that we are going after Keytruda, so to speak, but I would say that we are definitely evolving,” Jain told Fierce. “We are making sure that we understand that historical knowledge, understand the lessons that we need to learn, and then keep developing better therapies for patients.”
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