January 7, 2021 - Patients with pancreatic ductal adenocarcinoma who were treated with a 920 mg dose of SM-88 were less likely to experience a change in tumor texture and were found to have more favorable outcomes, according to results from a phase 2 dose-escalation trial.
Patients with pancreatic ductal adenocarcinoma (PDAC) who were treated with a 920 mg dose of SM-88 (racemetyrosine) were less likely to experience a change in tumor texture and were found to have more favorable outcomes, according to results from a phase 2 dose-escalation trial (NCT03512756) published in the Journal of Clinical Oncology.1
Investigators found that patients whose biggest lesions demonstrated more significant changes in texture at follow-up compared with baseline were more likely to experience disease progression (standard deviation in progressive disease [n = 10] vs stable disease [n = 7 and n = 1 N/A]; -0.07 vs -0.25; P = 0.05).
Additionally, greater changes in tumor texture were linked with poor survival at 180 days (skewness: Chi-Square = 4.81; P = .03; HR = 4.1 for above median Skewssf3). Six patients who developed new lesions experienced negative changes in follow-up kurtosis compared with baseline, while 12 patients did not (mean kurtosis, -0.67 vs +2.63; P = .05).
A greater change in tumor texture on follow-up versus baseline scans was observed in patients who received 460 mg of SM-88 compared with those who received the 920-mg dose (MPPLD = -0.29; MPPHD = -0.04; P = .05), which indicated that the higher dose of SM-88 resulted in more tumor stability.
“Tumor lesions in subjects on 920 mg of SM-88 were less likely to show a chance in tumor texture and were associated with better outcomes,” study author Allyson J. Ocean, MD, an associate professor of medicine at Weill Cornell Medicine and NewYork-Presbyterian, and colleagues wrote. “Using radiomic QTA [Quantitative Textural Analysis], less tumor texture variability from baseline may be associated with better outcomes in PDAC subjects.”
In previous research, the dysfunctional tyrosine derivative SM-88 has been shown to elicit promising efficacy with acceptable tolerability. Through the use of QTA, investigators have revealed noninvasive biomarkers that correlate with prognostic signatures of response in PDAC. Because prior radiomic data collected from patients who were administered SM-88 demonstrated a positive correlation between circulating tumor cells and baseline tumor texture, investigators set out examine the radiomic changes associated with SM-88.
Investigators conducted a retrospective evaluation of 18 patients with PDAC who had received more than 1 previous therapy. To be eligible for participation, patients had to have an ECOG performance status of 0-1, as well as baseline and follow-up contrast enhanced computed tomography (CT). No restrictions were in place regarding the size, number, or location of metastases.
In the trial, participants received more than 1 cycle of treatment with SM-88 at 1 of 2 doses that were given orally, once daily: 460 mg (n = 8) or 920 mg (n = 10). The QTA platform was used to evaluate CTs for tumor texture, and investigators used portal venous phase images to identify the largest metastases present in each patient.
“A region of interest was posited on the axial slice with the longest tumor diameter and features automatically generated using voxel resampling to correct for scanner variability across subjects and time points,” the authors wrote. Findings were showcased as histogram frequency curves of pixel densities and investigators conducted HFC analysis at spatial scale filters that ranged from none, to fine, to coarse texture.
In August 2020, the FDA granted an orphan drug designation to SM-88 as a treatment for patients with pancreatic cancer. Results from the phase 2 TYME-88-Panc trial showed that SM-88 resulted in a median overall survival of 6.4 months in patients with advanced pancreatic cancer.2,3 Moreover, among those who at least achieved disease stability, the agent resulted in a 92% reduction in the risk of death (HR, 0.08; P = .02). The clinical benefit rate of stable disease or better per RECIST criteria was 44% with available imaging; this benefit proved to be durable.
1. Ocean AL, Korn RL, Kim S, et al. Radiomic texture analysis correlates with PDAC patient outcomes on SM-88. J Clin Oncol. 2020;38(suppl 15):e16776. doi:10.1200/JCO.2020.38.15_suppl.e16776
2. TYME presents updated data at ESMO GI 2019 from TYME-88-Panc phase II study demonstrating encouraging overall survival trends in patients with advanced pancreatic cancer. News release. Tyme Technologies, Inc. July 5, 2019. Accessed December 23, 2020. https://bit.ly/2xNYEjr.
3. Noel MS, Wang-Gillam A, Ocean AJ, et al. SM-88 therapy in high-risk poor prognosis pancreatic cancer (PDAC). Ann Oncol. 2019;30(suppl 4):IV16. doi:10.1093/annonc/mdz155.058