SM-88 Moves Forward in HopES Sarcoma Trial

The interim futility review for the phase 2 HopES Sarcoma trial was positive and will continue to evaluate SM-88 for patients with Ewing sarcoma and other high-risk sarcomas.

The interim futility review for the phase 2 HopES Sarcoma trial (NCT03778996) was positive and will continue to evaluate SM-88 (racemetyrosine) for patients with Ewing sarcoma and other high-risk sarcomas, according to an announcement from Tyme Technologies.1

The interim futility review was completed in July 2020, the company stated. The study protocol will continue as planned based on data from the trial and recommendations of Sant Chawla, MD, FRACP, principal investigator of the HopES Sarcoma trial.

“It is evident that the salvage cohort will pass the futility test and meet the criteria for expansion,” Chawla, who is the founder of the Sarcoma Oncology Center, stated in the press release.

The next read out of the trial is anticipated in 2021.

“We are pleased to have reached this important point in the HopES Sarcoma trial and now await the final results of the trial to determine the potential of oral SM-88 in high-risk sarcomas in an effort to improve the lives of these patients with, what we believe could be, a better safer approach,” Giuseppe Del Priore, MD, MPH, chief medical officer at TYME, stated in the press release.

Systemic treatment for patients with sarcoma remains a current area of unmet need in which there is a significant opportunity for drug development. More than 12,000 patients are diagnosed with sarcoma each year, and without effective treatment options.

The open-label, phase 2 HopES Sarcoma trial is evaluating the safety and efficacy of SM-88 with methoxsalen, phenytoin, and sirolimus as conditioning therapy. A total of 24 patients will be enrolled into 1 of 2 cohorts. The first cohort will evaluate SM-88 as maintenance monotherapy following standard primary or palliative therapy for patients with high-risk Ewing sarcoma. The second cohort will evaluate SM-88 as salvage monotherapy for patients with advanced sarcoma.

Patient dosing began in January 2020.

The primary end points of the trial include overall response rate, stable disease rate, and progression-free survival. Key secondary end points include duration of response, overall survival, clinical benefit rate using RECIST v1.1 criteria, and the incidence of treatment-emergent adverse effects (AEs).

SM-88 is an oral investigational modified proprietary tyrosine derivative that was designed to interrupt the metabolic processes of cancer cells by breaking down the cells’ evasion and lead to cell death through oxidative stress and exposure to the immune system.

Clinical data have demonstrated encouraging responses across 15 malignancies, including cancers of the pancreas, lung, breast, and prostate, as well as sarcoma with minimal grade 3 or higher AEs.

The agent is not approved by the FDA for any indication in any disease. However, on August 3, 2020, the FDA granted an orphan drug designation to SM-88 as a treatment for patients with pancreatic cancer.2

In May 2020, updated results from the phase 2 TYME-88-Panc study were presented during the 2019 World Congress on Gastrointestinal Cancer. In the multicenter, open-label, 2-part trial, SM-88 was evaluated in patients with pancreatic ductal adenocarcinoma who had radiographic progressive disease, received 1 or more prior lines of treatment, and had an ECOG performance status of 0 to 2. In the study, patients were randomized to receive 460 mg daily or 920 mg daily of SM-88. All patients received daily methoxsalen at 10 mg, daily phenytoin at 50 mg, and sirolimus at 0.5 mg daily.

The updated results showed that treatment with SM-88 led to a median overall survival of 6.4 months in patients with advanced pancreatic cancer.3

Additionally, the RECIST clinical benefit rate (CBR) of stable disease (SD) or better was 44% with available imaging. A 92% reduction in the risk of death was reported in patients who had at least reached SD (HR, 0.08; P = .02). Moreover, the CBR was found to be durable, with the majority of patients who received SM-88 continuing to experience SD or better at 7 months or longer.

In terms of safety, serious AEs (SAEs) considered to be potentially related to SM-88 were reported in 4% of the intent-to-treat (ITT) group; these toxicities included abdominal pain, arthralgia, and hypotension. One patient who experienced an SAE continued on therapy. Ninety-four percent of patients in the ITT group experienced all-grade AEs; 17% of these were those to potentially be related to the study drug, and 12% of the events were grade 3/4.

References

1. TYME announces outcome of interim futility review for HopES sarcoma phase II study. News release. TYME. Published August 11, 2020. August 13, 2020. bit.ly/3ix2wue

2. TYME announces orphan drug designation for SM-88 as potential treatment for patients with pancreatic cancer. News release. TYME Technologies, Inc. August 3, 2020. Accessed August 13, 2020. https://bwnews.pr/31dn0RP.

3. TYME announces first patient dosed in TYME-88-Panc pivotal trial to evaluate SM-88 as oral treatment for patients with metastatic pancreatic cancer. News release. Published January 8, 2020. Accessed August 13, 2020. https://bit.ly/2PPei74.