[Editors Note – The following is a guest post that originally appeared almost a year ago. It is about everyone’s favorite reverse-merger pink sheet Coronacrapper-turning-Cancercon, Cytodyn (CYDY) from @B4UConsent, a real life patient with tremendous insight into drug development from both the patient and the clinical trial management perspectives. Given this morning’s nonsensical press release from Cytodyn, it is timely to re-up her thoughts.]
BuyersStrike has generously invited me – patient, investor, blogger at B4UConsent – back to do a guest post on CytoDyn’s TNBC delusions. Happy to help!
Today we sink from the height of scientific rigor and strategic foresight we witnessed with Roche’s IMpassion program to the sewage ditch that is CytoDyn’s attempt to take on – wait for it – triple-negative breast cancer (TNBC). TNBC is, for the uninitiated, the rarest breast cancer subtype, exhibiting no hormone receptors nor overexpressing the HER2 protein, which make patients ineligible for anti-hormonal agents or HER2-targeted agents. Further, this tends to be an aggressive subtype that occurs in younger patients, and it’s associated with the poorest outcomes.
Historically, while TNBC patients have had few treatment options beyond chemo, there have been advances, particularly with immunotherapy. Roche received an accelerated approval for the combination of atezolizumab plus the chemo drug Abraxane, to be used in the first line. Sacituzumab govitecan, from Immunomedics (IMMU) more recently received accelerated approval in third line. Atezo/Abraxane is the standout here, and I have my reservations about sac gov, but there’s no disputing that these accelerated approvals were hard-won on PFS (progression free survival) data. Roche and Immunomedics are now just left to sweat out the wait on those OS (overall survival) numbers.
In contrast, CytoDyn got rid of a fake tumor engrafted on a mouse that one time.
And since in the fever dreams of its retail fanbase, and delusional (at best) management team, leronlimab has already “cured” COVID and HIV, with GvHD and NASH (and MS and Alzheimers, and on and on and on) on deck, why not throw TNBC in the mix? It’s not like it’s hard to design, recruit and run a cancer trial. CytoDyn is generously “keep[ing] the FDA current” on their miracle outcomes, which seem largely limited to meaningless, outdated lab markers (CTCs, really?) and not the more meaningful outcomes we in cancer are all familiar with, things like, “Tumor in lung got 31% smaller.” I’m sure our friends at the Agency are eagerly anticipating these updates and sending them straight to voicemail.
The most telling press release about the garbage this company is peddling is from January 13.
They reference two patients, one of whom is apparently enrolled in the company’s phase 1b/2 study which enrolls previously untreated metastatic breast cancer patients. You can tell a patient to drink more water in the first-line setting and get at least a modest response, which is why it should be a GCP violation to enroll subjects first-line for completely unproven drugs. You get one shot at first-line, one chance to maximize response and the duration of response. We know response rates get lower with each line of treatment.
In this case, the company felt compelled to announce that their first TNBC subject had a reduction in circulating tumor cells (CTCs). This is a) not an endpoint and b) not clinically relevant. No one does CTC tests, and they were never adopted widely because they were useless. They were never sensitive enough; you could be a walking tumor and have a CTC of 0. Plenty of metastatic patients have CTCs of 0, and a CTC result higher than 5 would signal full-on death watch. A more modern and useful marker would be ctDNA, which are small fragments of tumor that are used in the liquid biopsy tests we have from Guardant and Foundation Medicine.
Guess what else? “This patient’s data also demonstrated tumor shrinkage of >20% after just a few weeks of treatment.” Greater than 20%, that sounds good, right? It’s actually not. It means the disease has remained stable. In cancer, we use one guideline to interpret tumor size and response on scans: it’s called RECIST 1.1, and the rules are very clear. As a former medical writer on oncology trials, I can recite them in my sleep: a complete disappearance of disease is a Complete Response, or CR; reduction in disease >25% is a partial response, or PR; change in tumor measurement <25% but not increasing in size by more than 25% is defined as stable disease, which is NOT considered a response; and increase in tumor measurements by >25% is progressive disease, or PD.
So by the accepted laws of oncology, this patient is an SD. The CTCs are meaningless.
And what of the second patient?
She was not enrolled in a trial. She received treatment under an “emergency IND protocol” and is described as having “HER2+ metastatic, stage 4, MBC” and “showed no sign of new metastatic spots in the liver, lung and brain during the treatment with leronlimab.” Yeah, no new lesions is always nice, but what about the lesions she had at baseline? Subsequent press releases also suggest that this patient was receiving other treatment concurrently, so how could we attribute anything positive to the leronlimab?
This nonsense concludes with, “This strong data confirms the power of leronlimab as a CCR5 inhibitor for patients living with mTNBC, and is clearly replicating early animal study results that demonstrated 98% elimination of metastases.” (Emphasis mine.)
What’s that, now? That little mouse had what would probably be classed as a CR. These two patients didn’t even respond.
But why stop at TNBC when the data are so compelling? That’s a tiny little sliver of the cancer population. Aren’t there a lot more cancers to cure and patients, shareholders and innocent bystanders to manipulate?
That brings us to the basket trial, open to all solid tumors, which seems to have just started enrolling a few days ago. “All solid tumors” will apparently be represented in a 30-subject phase 2 at one site, something called “Quest Clinical Research” in San Francisco. Just the name evokes the echelons of scientific development, no?
Let’s review the primary endpoints for this “trial” together, shall we?
- Number, frequency, and severity of adverse events (AEs)
- Incidence of abnormal laboratory tests results
- Changes in Eastern Cooperative Oncology Group (ECOG) performance status from baseline to subsequent scheduled visits
Are 1 and 2 not the same? And … what is 3 supposed to demonstrate? That is not an endpoint for approval in oncology. The enrollment criteria specify an ECOG status of 0-1 (that’s fully active to slightly less active; by 2, patients are getting pretty debilitated). So we’re looking at a phase 2 with no PFS endpoint. This study is exposed as even more of a sham by a line in the study description section:
Subjects participating in this study will be allowed to receive/continue standard-of-care chemotherapy or radotherapy [sic] as per the dosing schedule included on the package insert.
Let me get this straight. Subjects have the option of staying on therapies that are already working and just adding an experimental agent. What exactly is being tested here? Who would enroll in something like this, and why would anyone let them? Are they trying to design a “study” that can’t fail by deliberately rejecting the efficacy and enrollment standards by which a whole industry abides?
Though we don’t have answers, we do have a lesson: stay away from this bioturd. At least the mouse made it out.
Thanks again to BuyersStrike for having me.