Abstract
BackgroundAndrogen deprivation therapy (ADT) is standard treatment for rising PSA with/without circulating tumor cells (CTCs) but adverse events (AEs) limit patient acceptance. We report results of SM-88 (D,L-alpha-metyrosine; racemetyrosine [USAN]) in combination with a CYP3A4 inducer, mTOR inhibitor and catalyst that does not lower testosterone (T). MethodsPhase 2 with a rising PSA (per PCWG3), no disease on imaging and detectable CTCs. ResultsFrom Sept 2016-April 2019, 35 subjects consented; 23 evaluable (completed >1 cycle); 60.9% were post RT. Mean age 70.6; BMI 28.9; 21.7% black. Mean T rose (319.1 to 346.0ng/dL p=0.08) over 12 weeks. Subjects did not report side effects commonly associated with hormone suppression. Assessments of EORTC measured domains sexual health, overall health, and quality of life remained stable, with depression, hot flushes, and enlarged breast reported as “Not at all” (remained at 1). There was no detectable worsening in any domain of EORTC QLQ-C30 or QLQ-PR25. No clinically significant changes were seen in weight, hct, glu, urinary N telopeptide, MAP (in normotensives and hypertensives), heart rate, Ca++, LDH, bsAlkPhos, triglycerides, albumin, or QTc. NLR decreased at the end of cycle 1 in 75% of those with radiographic and/or PSA progression vs 53% of those who did not. 15/23 (65.2%) subjects reported experiencing an AE. 1 unrelated Grade 3; 18/35 (51.4%) at least possibly related to drug. No AEs were related to T levels. There were no skeletal or cardiovascular events. From initial diagnosis of PSA rise 100% (23/23) remained metastases free. PSA declined (4% 1/23) stabilized (83% 19/23) or rose (13% 3/23). 56.5% (13/23) subjects experienced an improvement in median PSA DT. Median DT time improved from 6.2 to 8.0 months for all subjects completing 3 cycles of therapy. CTCs were > 5 in 100% at baseline. After 12 weeks, there was a 65.3% (-100% to -8.8%) median CTC decrease from baseline (n=18), with all subjects having CTC counts below baseline and 2 undetectable. ConclusionsSM-88 may delay the start of HT and be useful when normal T is preferred. QOL was maintained without ADT AEs. Favorable effects on PSA and CTCs kinetics were observed consistent with a favorable treatment effect. Trials to confirm these benefits are planned. Clinical trial identificationNCT02796898. Legal entity responsible for the studyTyme Inc. FundingTyme Inc. DisclosureG. Del Priore: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Tyme Inc. G.H. Sokol: Advisory / Consultancy: Tyme Inc. A. Vandell: Full / Part-time employment: Tyme Inc. All other authors have declared no conflicts of interest.
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