The best treatment candidate for keeping me alive that I’m aware of is Moderna’s mRNA-4157 personalized cancer vaccine: in very early data from 2020, a 10-person dosing study found that the treatment “shrank tumors in five patients with head and neck cancer (50%), eliminating the tumors in two of those patients.” By recurrent / metastatic head and neck squamous cell carcinoma (R / M HNSCC) standards, that’s spectacular, so I perked up on Monday when Moderna announced phased 1b trial results showing that, of 22 patients who were dosed, two-thirds saw at least some “disease control” (meaning that their tumors stayed about the same size or shrank), and two saw their tumors disappear altogether. Pretty much everyone who has R / M HNSCC dies, and R / M HNSCC doesn’t readily respond to treatment, so anything with effectiveness like this is important.

Still, this is not so great: “About 27% of those receiving the vaccine showed an overall response rate, or ORR, with 3.4 months of progression-free survival, or PFS, and 24.6 months of overall survival, or OS.” Having only three and a half extra months without tumor progression is good, but not something like, say, three years. And surviving 24.6 months is nice—the R / M HNSCC median lifespan is just twelve months after diagnosis—but could, again, be longer. Moreover, on a personal level, if I’m going to survive I need access as soon as possible, and, at least as of January, one oncologist who works closely with Moderna told me she’s not aware of any phase 2 trial planned for 2024. That was three months ago, so things might’ve changed since.

I also note this, from the poster presentation: “Part C of this study enrolled patients ¬18 years old with checkpoint inhibitor (CPI)-naive, recurrent / metastatic HPV- HNSCC.” “CPI-naïve” means patients who haven’t receive pembrolizumab (Keytruda), which I have. If the phase 2 trial also requires that I be CPI-naïve, I’ll be out of luck. While phase 2 drugs can sometimes be petitioned for compassionate use if a terminal patient doesn’t qualify for a trial, it’s less likely that a personalized, tumor-specific treatment that requires more intensive preparation than, say, mailing an IV bag of a batch-produced drug, will be acquirable.

There’s another ominous phrase in the presentation, too: “Randomized assessment of the mRNA-4157 + pembrolizumab treatment effect in the advanced disease setting may be warranted.” So there will probably be a placebo group that gets only pembro, which I’ve already failed.

I don’t understand why the results so far aren’t enough for accelerated FDA approval, given the grim prognosis for R / M HNSCC, the limited treatments available, and the safety of mRNA-4157. It could be that Moderna doesn’t have the capacity to mass produce mRNA vaccines yet—the company is building a factory in Massachusetts that won’t come online until 2025—though that article also notes that “In 2018, the company opened a $110 million, 200,000-square-foot mRNA plant in Norwood.” Part of the approval process could I guess be proving not only efficacy, but the ability to mass-produce the vaccine; so Moderna won’t file paperwork for approval until the facility is running, which means that patients like myself, who so desperately need better treatment options now, will likely not be running at all by then, having run out of time.

Right now I’m about to begin a clinical trial of Seagen’s PDL1V antibody drug conjugate, which is good, though it’s unclear whether I’ll get dosed soon enough for PDL1V to work well enough to stop the tumors in my neck from breaching critical structures. Knowing what I know now, I probably should’ve gotten chemo immediately upon getting the tumor-growth news on March 13. But I didn’t for somewhat complex reasons I’ll explain in the next essay—primarily because PDL1V, like many clinical trials, has an arbitrary-seeming limit on the number of “systemic therapies” a patient can have undergone. Cruelly, the clinicaltrials.gov page for PDL1V doesn’t even appear to list a lines-of-therapy limitation, which means patients like me have to call sites to eventually get the news. That should be publicly stated, so as not to waste everyone’s time. But “wasting time” is normal, though maddening, in clinical trials. Ultimately, the time that matters to the sponsoring drug companies is not the patient’s, but the persnickety FDA’s.

Overall, we should be working to have drugs like mRNA-4157 get much, much faster approval, rather than leaving people dead and dying at the gates of oncology clinical trials. Particularly frustrating is the unavailability of mRNA-4157 when considered with the other highly promising, low-side-effect, unavailable drugs in the pipeline: petosemtamab / MCLA-158 (which I just failed), Purple Biotech’s NT219 small molecule, the Seagen (now Pfizer) ADCs like PDL1V.

The real benefit is likely to come by combining therapies with differing mechanisms of action. Getting mRNA-4157 or petosemtamab or PDL1v as monotherapies or duotherapies is nice, but R / M HNSCC has time to adapt to and defeat treatment. Using multiple drugs at once might make a larger number of “complete responses”—cures—conceivable. Instead, playing whack-a-mole with cancer by trying a new drug every time an old drug pressures the cancer to mutate, creates a recursive loop until there are no more drugs to try, or the next drug doesn’t work. It’s possible, though unlikely, that some unforeseen interaction among treatments will prove fatal, but so what? R / M HNSCC is already fatal. I should have the right to try, without the FDA blocking me and thousands of other dying patients. We need faster treatments, not more trials that let the dying languish.

In other HNSCC news, Transgene is moving its personalized vaccine to a phase 2 trial. That vaccine targeted at patients who have an initial surgery and then want to prevent recurrence; in the phase 1 trial, patients “were randomized to one of two treatment arms: one in which patients received repeated injections of the personalized vaccine as an additional adjuvant therapy and another in which they did not receive any additional adjuvant therapy.” No patients who received the vaccine relapsed; three of those who didn’t, did. “Roughly 40 percent of head and neck cancer patients are expected to experience cancer recurrence within two years of surgery and adjuvant therapy, according to Transgene.” If that TG4050 vaccine had been available in October 2022, when I had my initial surgery, I’d probably still have a tongue, be able to work, and look forward to spending years if not decades with Bess. Instead, every day is a fight and every month I’m alive a surprise. The technology exists but we’re slow-walking it to patients, which is insane.