A lot of doctors have been reading the squamous cell carcinoma saga, and they keep asking for clinical detail about what’s going on. Although they don’t literally say: “The emotional love story is great and all, but we really want to know about disease progression and the clinical plan,” I get that that’s what they’re yearning for deep in their souls. It doesn’t make them unromantic—if anything, their commitment to medicine is equivalent to that of a great love, outlasting most actual relationships (if the physician divorce rate is to be believed).

On Wednesday I started a clinical trial of petosemtamab (MCLA-158) at the University of California-San Diego Medical Center. Early data is promising: 31 out of 43 patients in a previous trial saw their tumors either shrink or stay the same size.* Relative to the recurrent / metastatic squamous cell carcinoma of the head and neck (R / M HNSCC) baseline, that’s really good! Relative to more successful cancer treatments, having only 16 out of 43 patients see their tumors shrink is—well, the math is what it is. Still, petosemtamab is a plausible path forward, and a plausible path forward didn’t exist until recently.

The article about early data says: “Of the patients who responded, the median [duration of response] DOR was 6.0 months.” If I—or, rather, my tumors—respond to petosemtamab, I can expect the treatment to keep the tumors in check for about six months. It’s possible to get lucky and have the petosemtamab affect the tumors longer, and it’s obviously also possible that petosemtamab will stop working before six months, if it works at all. From what I’ve gathered, the long-term plan for oncologists and patients is to combine petosemtamab with immunotherapies like pembrolizumab, and possibly with chemotherapies, to see if petosemtamab generates synergistic responses. I’m getting 1100mg of petosemtamab every two weeks; 1100mg and 1500mg doses are being tested.

Bess and I have also been thinking about what to do if two-month or three-month CT scans show petosemtamab failing to contain the tumors: Magrolimab is a possible answer. RAPA-201 at Hackensack University Medical Center is another. There are other clinical study drugs at UCSD that may be conceivable routes forward. A fecal transplant from a pembrolizumab responder combined with additional pembrolizumab is also possible: this sounds ridiculous but it’s a real line of research, especially in Europe. A casual search shows articles like “The potential of fecal microbiota transplantation in oncology” and “Efficacy of Responder-derived Fecal Microbiota Transplant (R-FMT) and Pembrolizumab in Anti-PD-1 Refractory Patients with Advanced Melanoma.” Most research appears to be in melanoma thus far, but not all of it. Changing the tumor microenvironment might lead to significantly improved responses to treatments, which means that the unreliable markers clinicians currently use to guide treatment might not matter as much as the cellular environment around the tumor.

A patient who isn’t responding to a life-saving treatment like pembrolizumab might become someone who does, just by having the poop from a responder put in their colon via colonoscopy. Sign me up! This potential door was opened by Bess and Dr. Jamie Bering, a Mayo gastroenterologist who is currently wading through tons of red tape to both get the approval to perform the treatment on me, and to find a responder to “donate.” Both these things require FDA and IRB approval—a glacially slow process—and, two months in, neither have given the thumbs up. Right now, my default path is dying within twelve months and more likely eight (in July, I didn’t know how fast the cancer was moving or whether chemo would temporarily halt it, and I consider all the time since the massive May surgery to be “bonus time”), so there’s no real downside to experimenting.

As far as I can tell, petosemtamab shows some similarities to another antibody called BCA101, since both drugs target EGFR mutations. BCA101 wasn’t available when Bess and I were working to find the right clinical trials, so the petosemtamab trial is where I’m at. Bess is working on a monster essay about the clinical trial process, which is full of detail about the insanity of the process from the patient’s perspective. Though it seems odd to me, petosemtamab is presently only available at UCSD in the United States, despite there being a bunch of trial sites in Europe. There’s presumably a behind-the-scenes reason.

I don’t think I’ve stated clearly and in order what happened, and how it happened:

* Late summer 2022: I notice a sensitive area in the back left side of my tongue. I suspect I bit the tongue by accident and that it’s slow to heal. But the area doesn’t heal, and I eventually see a community ear, nose and throat (ENT) doctor named Jacob Ossoff at Valley ENT in Scottsdale. He orders a biopsy. The first attempt at biopsy is unsuccessful due to the excruciating pain from essentially trying to cut out a piece of my tongue with minimal numbing medication. Bess canvasses doctors online, and apparently “not much numbing medication” is standard of care and many other doctors think ENTs are sadists. Around Sept. 26 we get the biopsy news: squamous cell carcinoma. Ossoff and his partner refer me to Michael Hinni at the Mayo Clinic, who specializes in surgeries that include a “flap”—that is, taking a piece of muscle from another part of the body and implanting it into the tongue.

* Oct. 20, 2022: Dr. Hinni cuts out the carcinoma using a Co2 laser (very futuristic) and gets clean margins. No flap is necessary. The carcinoma is 9mm deep and displays “perineural invasion,” which means that it’s invaded nerves in the tongue. These count as “high-risk features” that argue for radiation. Given what’s happened since, I wish we’d done chemo along with the radiation, but at the time I was pleased to avoid chemo. I get to leave the hospital the day after surgery. Physician notes observe: “T2N0M0 oral tongue SCC with PNI, LVSI, and aggressive pattern of invasion status post left partial glossectomy and left modified radical neck dissection receiving adjuvant RT.”

* Dec. 1, 2022 to Jan. 13, 2023: Intensity Modulated Radiation Therapy (IMRT); 30 fractions; 6,000 cGy.

* April 26, 2023: PET scan is hot, and we hope it’s osteomyelitis. A fine needle biopsy and a core biopsy are both inconclusive. A surgical biopsy on May 11 reveals a cancer recurrence. Throughout May, I get steadily more severe headaches and steadily greater fatigue.

* May 22, 2023: Start pembrolizumab.

* May 25, 2023: Total glossectomy; Dr. Hinni leads the surgery and his colleague, Tom Nagle, makes the flap from muscle in my leg. This surgery was supposed to be a hemiglossectomy—losing half the tongue—but the tumor had sprinted across my tongue and invaded both lingual arteries (the main blood vessels supplying the tongue), so my entire tongue had to be removed. So I woke up with the “flap” instead of a tongue. It’s better than dying, although I wasn’t so sure at the time. I understood going in that the surgery plan was a plan, not a guarantee.

*July 21, 2023: A CT scan shows a recurrence in the neck and metastases in the lungs. The CT was supposed to be checking on post -operative bone healing, to see whether I could do any jaw-stretching exercises after the surgery. Bess and I had spent a lot of time in June and July trying to decide whether we should add chemo on top of pembrolizumab; oddly, no one has rigorously tested whether chemo is helpful for people with R / M HNSCC who get salvage surgery with clean margins. We know that chemo kills some HNSCC cells, even if it does not remove gross tumors. So, in theory, chemo may remove errant cancer cells. But we don’t have firm evidence. Some oncologists said we should do pembrolizumab only; some said chemo is a 50-50 option, or a reasonable option, and we elected for it. Life moved faster than us, however.

* July 24, 2023: Pembrolizumab/chemo: Paxitaxel and Carbolatin.

* August 14, 2023: Another pembrolizumab/chemo round.

* Sept. 5: I’m scheduled for another round here, but instead we have a six-week washout period for the petosemtamab trial. So I skip the pembro and chemo. I do okay, physically, until around Sept. 15, when headaches begin to assault me again, and fatigue increases.

The petosemtamab exclusion criteria include: “Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is longer of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity ( e.g. mitomycin C,nitrosoureas), or anticancer immunotherapies, a washout period of 6 weeks is required.” So I thought I’d only have a four-week washout period, since carboplatin and paclitaxel have relatively short half lives. I did fairly well for four weeks after pembro/chemo, and then the headaches started up.

* September 27: First dose of petosemtamab. Ongoing headaches make daily life a challenge. Petosemtamab doesn’t appear to generate any side effects, but by Oct. 3 I get a gnarly rash on my chest, back, and face, with extensive itching on the face.

* There’s a copy of the presentation itself here.