SM-88 Shows Promise in Advanced Pancreatic Cancer | OncLive

SM-88 Shows Promise in Advanced Pancreatic Cancer

January 31, 2019

Allyson J. Ocean, MD, discusses the potential impact of SM-88 in the treatment of patients with advanced pancreatic cancer and highlights a platform that patients can use to stay updated on the latest research in the field.

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.

OncLive: Please provide background on the novel regimen SM-88.

Could you highlight the data seen with this agent?

What is the toxicity profile of SM-88?

SM-88 was recently added to the Precision Promise platform. What are your thoughts on this?

What are some challenges with finding effective therapies in the third-line setting and beyond?

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.Ocean: 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.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.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.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.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.

Is there anything else you would like to add?

When you look at clinical trials in this patient population, we need to include patients with an ECOG performance status of 2. We also need to be careful about the enrollment in terms of the wash-out period and try to get these patients on therapy quicker. I like this approach because patients can quickly go on to the next best therapy.[I am excited] to talk to community oncologists about Let's Win! Pancreatic Cancer, a nonprofit digital platform that crowdsources treatment options for patients with pancreatic cancer. It connects the patients with the doctors and researchers in real time, and highlights clinical trials and research efforts that are out there. It is also a framework for patients to connect with each other. Many times, in pancreatic cancer, you only hear the bad stories, but there are a lot of good stories of patients who are living longer than what the numbers say. We would like to eventually study these patients and find out what makes them outliers. Why do they respond better? We will soon be compiling that information into a database.

This platform is a vehicle that gives people hope, and that is really important. It is online, easy to access, and patients get a lot of hopeful information from it. All of the information on Let's Win! [Pancreatic Cancer] is vetted by pancreatic cancer experts. We hope this will help spread awareness in the space.

Patients are more empowered when they have more information about their disease. When patients are struck with pancreatic cancer, they are lost and devastated. Sometimes, they only read negative information. Our goal is to provide science to the patients in a way that gives them actionable information. They can bring this information to their doctor and say, "Hey, I saw that there is a drug that targets this pathway. Could I go on this trial?" Patients do not even know what questions to ask; this is a really easy and straightforward [way for them to get necessary information].

Noel MS, Wang-Gillam A, Ocean AJ, et al. Phase II trial of SM-88 in patients with metastatic pancreatic cancer: preliminary results of the first stage. J Clin Oncol. 2019;37(suppl; abstr 200). meetinglibrary.asco.org/record/168775/abstract.


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