Allyson Ocean, MD
SM-88, a novel oral compound, has shown encouraging efficacy in early-stage data, said Allyson, J. Ocean, MD, but most importantly, the agent seems to be very well tolerated in patients with metastatic pancreatic cancer.
In an open-label, single-arm, phase II study presented at the 2019 Gastrointestinal Cancers Symposium, 28 evaluable patients with initial stage II, III, or IV disease, were treated with the regimen, which is comprised of a tyrosine derivative (D,L-alpha-metyrosine), an mTOR inhibitor (sirolimus), a CYP3a4 inducer (phenytoin), and an oxidative stress catalyst (methoxsalen). After a median follow-up of 4.3 months after treatment initiation, 67.8% of patients were alive and still on treatment, said Ocean, who is an associate professor of clinical medicine at Weill Cornell Medicine and NewYork-Presbyterian.
“It is an important drug in this space because we need better therapies and if patients are in the second and third lines of treatment, they likely cannot tolerate chemotherapy—especially at the standard dose,” said Ocean. “To have a new compound with a really good side effect profile is something that is important.”
Overall, 84.2% of patients experienced a treatment-emergent adverse event (AE) related to SM-88, but Ocean noted that only 1 or 2 patients demonstrated a grade 3/4 event; 16.2% of AEs were considered possibly related to the study regimen.
In an interview with OncLive
, Ocean discussed the potential impact of SM-88 in the treatment of patients with advanced pancreatic cancer and highlighted a platform that patients can use to stay updated on the latest research in the field.
OncLive: Please provide background on the novel regimen SM-88.
: Patients with advanced pancreatic cancer have very few effective treatment options, and I feel that we desperately need new options for these patients. Many patients are seeing later lines of therapy, so we need more effective therapies after the first and second lines. I think SM-88 is a novel compound; it is an oral agent, which is important. I explain to my patients that it's novel because it targets the metabolic aspects of cancer growth. It is a dysfunctional amino acid that acts like a decoy to trick the cancer cell into being fed, but it is not being fed. Eventually, SM-88 disrupts protein synthesis so the cell ultimately dies.
Could you highlight the data seen with this agent?
The trial that is being presented included 38 patients, 28 of which were evaluable. The key points to highlight, given that it is an early study, are that 4.5 months into evaluation, almost 70% of the patients were alive and on therapy. This shows that heavily pretreated populations—and a majority of the patients had [three lines] or more of therapy—maintained stable disease. This is very important. The other thing to point out is that most patients come off protocol not for progression of disease, but because of disease-related complications.
What is the toxicity profile of SM-88?
It is really important to point out that the toxicity profile is very favorable. I have had a couple of patients on the medication who have told me they feel better, have more energy, and they compare the treatment with chemotherapy without the toxicities. In fact, there were only 1 or 2 grade 3/4 AEs in this study; one was related to rash. Patients actually stated that they felt better and had a better quality of life. It is still early, and we cannot make any strong statements in terms of efficacy, but it is very encouraging to see a compound with early efficacy in late-stage pancreatic cancer. Now, we are able to offer an agent to our patients in a clinical trial framework that may improve outcomes and not make them sick.
SM-88 was recently added to the Precision Promise platform. What are your thoughts on this?
Because we have access through this trial to a large group of patients, it is great that SM-88 is now available to them. We can accrue faster that way and we can have more options for these patients who progress quickly on later lines of therapy. The fact that we are collaborating with a large organization is encouraging, and it is a good way to get this drug in testing the fastest.
What are some challenges with finding effective therapies in the third-line setting and beyond?
Some of the challenges we face with developing clinical trials are how to phase in performance status into what patients can tolerate in terms of therapies. Also, the screening period for patients is important, too, because most trials have a wash-out period from previous therapies. Sometimes that period is just too long in pancreatic cancer. The disease can progress so fast that patients do not even get a chance to try a novel compound. Therefore, clinical trial enrollment can decrease because of these criteria. There is basically a barrier to enrollment.