Phase I Study Of Oral Gz17-6.02 In Patients With Advanced Solid Tumors Or Lymphoma

Background: Botanical molecules, such as curcumin, have been extensively studied as a potential anti-cancer therapeutics. Research has recently identified a combination of three synthetically manufactured natural molecules for clinical study in oncology. An optimized ratio of isovanillin, harmine, and curcumin has shown preclinical evidence of in-vitro and in-vivo activity with evidence of super enhancer modulation providing rationale for clinical study. Methods: Phase I, multicenter, open-label, dose-escalation, safety, pharmacodynamic and pharmacokinetic study of GZ17-6.02 given orally on a daily x 28 day of schedule in patients with advanced solid tumors or lymphoma. The dose escalation followed a standard 3+3 design. Thirty-six patients have accrued to the study, 24 in the dose escalation phase and 12 in the dose expansion phase at the recommended phase two dose (RP2D) of 375mg bid. Results: GZ17-6.02 has demonstrated to be generally well tolerated with an acceptable safety profile. Grade 3/4 transaminitis was observed in 6 out of 32 evaluable patients and was the dose limiting toxicity. Transaminitis was readily reversible upon discontinuation, no elevations of bilirubin were observed and 3 of the 6 cases of elevated transaminitis occurred above the RP2D. Grade 3/4 dizziness was observed in one patient. Two patients contracted COVID-19 while on study, though no dose interruptions or modifications were necessary. An investigator assessed partial response was reported in a patient with EGFR mutated Non-Small Cell Lung Cancer. Stable disease was observed in six additional patients at various dose levels within the study. Additional evidence of radiological tumor regression was also observed. Clinical benefit was observed in seven patients as assessed by investigators. Conclusions: GZ17-6.02 was biologically active and demonstrated an acceptable and manageable safety profile in a heavily pretreated patient population with various malignancies. This phase 1 data provides rational for further investigation in a phase 2 setting to determine GZ17-6.02’s safety and potential efficacy in defined patient populations, both as monotherapy and in combination with other therapeutics. Clinical trial identification: NCT03775525 Legal entity responsible for the study: Genzada Pharmaceuticals USA, Inc. Funding: Genzada Pharmaceuticals USA, Inc. Disclosure: R.P. Moore: Financial Interests, Personal and Institutional, Member: Genzada Pharmaceuticals. J. Bailes: Financial Interests, Personal and Institutional, Member: Genzada Pharmaceuticals. All other authors have declared no conflicts of interest.