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SM-88 Safe, Active in Nonmetastatic CRPC

Brandon Scalea
Published: Friday, Feb 22, 2019

Benjamin A. Gartrell, MD

Benjamin A. Gartrell, MD

Updated phase II data showed that SM-88 may be an effective option either before or as an additive to current prostate cancer therapies where normal testosterone may be preferred, as the agent may not worsen quality-of-life (QoL) parameters related to testosterone level, said Benjamin A. Gartrell, MD.

Results from the small prospective trial, which were presented at the 2019 Genitourinary Cancers Symposium, showed that 82% of patients treated with SM-88 experienced an improvement in prostate-specific antigen (PSA) doubling time. In addition, 67% of the patients who received SM-88 demonstrated a decline in circulating tumor cells (CTCs) of >30%. The overall median PSA doubling time at enrollment was 5.3 months and improved to 6.5 months after therapy (P = .02).

“One thing we are very interested in doing is taking a population of patients who are currently receiving androgen deprivation therapy (ADT) or hormonal therapy and figuring out if it is possible to delay the time until the patient needs hormonal therapy—that is what we are trying to do with SM-88,” said Gartrell, lead study author.

The drug compound also appeared to be well tolerated, with few associated adverse events (AEs) observed that are commonly reported with hormone therapy. In the study, 96% of patients reported no cases of hot flashes, 83% said they did not lose their sex drive, and 61% said that they did not see their sexual performance affected by treatment. In a post-therapy questionnaire, 74% reported their QoL as “excellent.”

In an interview with OncLive, Gartrell, an assistant professor of urology at Albert Einstein College of Medicine and a medical oncologist at Montefiore Medical Center, discussed the promise of SM-88 in this patient population, as well as other therapeutic options that are emerging for various prostate cancer subtypes.

OncLive: Please provide some background to SM-88.

Gartrell: SM-88 is a novel, oral, nonhormonal medicine that is being evaluated [as a treatment of patients with] prostate cancer. It is based on a novel derivative of the amino acid tyrosine. SM-88 is given in combination with 3 additional medicines that are all approved by the FDA, but they are given for noncancer indications. The hope is that SM-88 targets cancer metabolism, and we believe that it will have a negative effect on cancer cells but no impact on normal cells. We also expect it to have a great toxicity profile. 

What were the findings presented from this study?

This was a phase II trial of patients with nonmetastatic prostate cancer who had a rising PSA. Patients were given SM-88, and what we found was that there was a significant decrease in CTC. There was also a significant slowing of PSA rise, or you could call it a prolongation of PSA doubling time. 

What was the toxicity profile of the drug?

The [profile] was excellent. We believe that patients would like to avoid ADT, which is a hormonal medicine, for as long as possible. When men receive ADT, it means their testosterone is made to go very low. Therefore, typical AEs that we see are hot flashes, sexual side effects, weight gain, and loss of muscle and bone. There is certainly a decrease in QoL as well. SM-88 is a nonhormonal therapy and is not associated with any of these AEs. In this clinical trial, we did not see any of the typical hormone-associated AEs or any deterioration of QoL. 

What are the next steps for this research?

We expect that we will develop SM-88 in patients with nonmetastatic prostate cancer, specifically in those who have undergone local therapy for their disease and have a rising PSA. The current standard of care for these patients would be to initiate hormone therapy to lower testosterone, but we expect to develop a clinical trial where we will offer men [who are] in this situation SM-88 versus placebo. 

What other prostate cancer studies recently presented at the 2019 Genitourinary Cancers Symposium were you excited about?

This is a space that is becoming pretty crowded. We now have the approval of apalutamide (Erleada) for patients with nonmetastatic CRPC. We also have enzalutamide (Xtandi) [for the same indication].

In addition to that, the ARAMIS trial is now showing us good evidence for darolutamide. [This agent is being evaluated in] patients with nonmetastatic CRPC who have a rising PSA; these patients have a castrate level of testosterone, so by definition, their disease is castration-resistant. Darolutamide is a novel antiandrogen agent, and when added to ADT in ARAMIS, it was shown to have a significant benefit in prolonging metastases-free survival in these patients. The outcomes look very similar to what we saw with enzalutamide and apalutamide in the same population. The toxicity profile looks reassuring; darolutamide is generally a well-tolerated drug. 


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