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Hello again from Madrid, where we can tell you it’s Day 2 of the European Society for Medical Oncology’s annual meeting, but definitely not what day of the week it is. Perhaps some of the other nearly 40,000 people here can relate?
Enjoy today’s newsletter; we’ll be back with one more edition wrapping up the conference Monday afternoon. And on Thursday, join us for The STAT Recap, where we’ll catch you up on all the ESMO news you need to know, and answer your questions live.
In the meantime, we’re at [email protected] and [email protected].
Inside Moderna and Merck’s ‘presidential’ presentation
Adam Feuerstein/STAT
No surprise, the arena-sized room was packed with ESMO attendees eager to see Georgina Long of the Melanoma Institute Australia present the intismeran INTerpath-001 study results. The unfortunate data leak on Thursday made her talk less dramatic, but at the end, she received extended applause and a limited standing ovation.
Long summarized the intismeran results — a 42% reduction in the risk of disease recurrence and a 38% reduction in the risk of distant metastasis-free survival — as a “new benchmark for adjuvant treatment of melanoma.”
“More critically,” she added, “it establishes intismeran as a landmark advance in personalized cancer medicine.”
The full trial data will be published next month in the New England Journal of Medicine, Long also noted.
Inge Marie Svane of the University of Copenhagen, the discussant following the data presentation, was positive if not overly enthusiastic about the trial, describing the results as “compelling” and adding that they “mark a crucial moment for personalized cancer vaccines.”
But Svane also pointed to a number of outstanding questions, including whether there would be a survival benefit with intismeran, and what exactly was driving the vaccine’s benefit — was it the specific targeting of the neoantigens, or was it the general immune boost that studies have suggested mRNA vaccines provide?
She also took no position on the best way to treat the approximately 40% of higher risk melanoma patients enrolled in the study — a key debate with commercial implications. If intismeran is approved, it will compete against neoadjuvant immunotherapy, or treating patients before surgery. Svane laid out pros and cons of each approach, leaving the question of which will benefit patients more unanswered.
On mistrust and mRNA
The vast majority of the discussion about Merck and Moderna’s cancer vaccine centered on the quality of the data and the further application of individualized cancer therapies. But Toni Choueiri, of Dana-Farber Cancer Institute, raised an important point during an address in a special session all about mRNA vaccines.
Mistrust and misinformation, Choueiri said, “is a key challenge to adopting anything that is mRNA.”
It seems that many people who hold unfounded doubts about mRNA vaccines for infectious diseases separate the technology’s potential in cancer — no more so than the people running the U.S. health department. While the federal government is throwing its weight behind cancer vaccines, it’s also drastically cut funding for mRNA vaccine research for pathogens.
But Choueiri said the pandemic highlighted how widely and quickly myths can spread, citing 2022 survey data that indicated 15% of people falsely believed that the mRNA Covid-19 shots could alter human DNA.
The concern is that such misguided fears could have ripple effects to anything called a vaccine, particularly if it’s made with mRNA. Choueiri noted that some people have moved away from using “vaccine” when describing products like the Merck-Moderna treatment, instead calling it a personalized neoantigen therapy.
Moderna CEO Stéphane Bancel, speaking to STAT a couple of hours before the intismeran presentation, believes showing the benefits of an mRNA-based therapy in cancer — a disease that has affected a broad swath of Americans — will go a long way towards shifting perceptions of people who might have viewed mRNA in a negative way.
“I think the cancer treatment is going to help a lot,” Bancel said. “People will realize what we already know, that mRNA is a molecule that’s already in your body.”
An expanded use for Amgen’s Imdelltra in small cell lung cancer
The combination of Amgen’s Imdelltra plus Astrazeneca’s Imfinzi used as a maintenance regimen improved overall survival in patients with extensive-stage small cell lung cancer — a successful outcome that is expected to expand the commercial opportunity for Imdelltra in small cell lung cancer.
The presentation also drew a standing ovation from some in the room.
In the DeLLphi-305 study, the median overall survival for patients treated with Imdelltra and Imfinzi was just over 21 months compared to just under 13 months for patients receiving Imfinzi alone. Statistically, the doublet regimen reduced the risk of death by 58% compared to Imfinzi.
Cytokine release syndrome, a type of immune side effect, was reported by nearly half of the participants in the doublet arm, but the cases were mostly mild to moderate.
The 563 patients enrolled in the study had extensive-stage small cell lung cancer that had not yet progressed following first-line immunotherapy. The study was published simultaneously in the New England Journal of Medicine.
The results appear to set a new survival benchmark for maintenance therapy in small cell lung cancer. A previous study that combined Jazz Pharma’s Zepzelca with Roche’s Tecentriq reduced the risk of death by 27% compared to Tecentriq alone.
“The separation of the curves that we’re seeing here is not the kind of thing that we typically see in small cell lung cancer,” Jacob Sands of Dana-Farber Cancer Institute, who presented the data, told reporters. “These are extraordinary hazard ratios.”
Stephen Liu, a Georgetown University oncologist who was the study’s discussant, echoed that point.
If patients are eligible for the treatment approach, Liu said, “I can’t think of a subset where I would not want to offer this regimen.”
Astrazeneca’s bladder cancer push falls short
The neoadjuvant, or presurgical, use of Astrazeneca’s drug Imfinzi in patients with muscle-invasive bladder cancer reduced the risk of death by 42% compared to surgery alone. The risk of disease progression or death was reduced by 49% compared to surgery alone.
The positive results, however, don’t quite match the current standard of care.
Astrazeneca’s Phase 3 VOLGA study treated advanced bladder cancer patients with Imfinzi plus Pfizer’s Padcev before surgery, followed by Imfinzi after surgery, and compared their outcomes to patients who only underwent bladder surgery.
The study was published simultaneously in the New England Journal of Medicine.
At two years of follow up, 63% and 45% of the patients in the Imfinzi-Padcev and surgery only arms, respectively, were alive without tumor progression. Overall survival at the same time point favored the Imfinzi-Padcev group over surgery alone, with 78% and 69% of patients alive, respectively.
The VOLGA outcomes fell short of the current standard of care for the neoadjuvant treatment of muscle-invasive bladder cancer. Merck’s Keytruda plus Padcev reduced the risk of death by 50% and the risk of tumor progression by 60% compared to surgery alone.