Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Methods: ZN-d5-003 is a multicenter, international Phase 1/2 clinical trial evaluating single-agent oral ZN-d5 in relapsed or refractory AL amyloidosis subjects. In the Phase 1 part, the primary objectives are to determine the safety, tolerability and maximum tolerated dose of ZN-d5, and to determine the recommended Phase 2 dose. Cohorts of increasing doses (200mg; 400mg; 800mg; 1200mg; 1600mg QD) will enroll subjects based on Bayesian Optimum Interval (BOIN) design. In Phase 2, the primary objective is to assess the hematological response rate (HRR) among subjects with or without t(11;14) translocation. Bayesian Optimal Phase 2 (BOP2) design is implemented for interim efficacy monitoring. Key criteria for eligibility include the following: subjects must have a biopsy-confirmed diagnosis of AL amyloidosis, at least 1 and no more than 3 prior lines of therapy (including HSCT), adequate organ function and ECOG performance status of 0-2. All subjects must have measurable disease defined as dFLC of at least 20 mg/L; those considered for the trial will undergo bone marrow aspiration for assessment of t(11;14) status by FISH. Both t(11;14)-positive and -negative subjects are eligible for the study, however they will be separately analyzed for safety and efficacy. Subjects must have a history of organ involvement (current measurable organ disease is not required). Exclusion criteria include non-AL amyloidosis, diagnosis of multiple myeloma per 2014 IMWG criteria, or Mayo 2012 Stage IV disease. The study is expected to enroll up to approximately 140 subject at approximately 25 sites for phase 1, and at least 50 sites for phase 2.
Conclusion: This study will evaluate treatment of AL amyloidosis utilizing BCL-2 inhibition and will test the hypothesis of whether t(11;14) is a relevant predictive biomarker. Dose escalation cohorts are currently undergoing evaluation and the study is open to enrollment. Upon determination of a recommended phase 2 dose, the study will commence Phase 2. Clinical trial: NCT05199337.
Disclosures: Kastritis: Takeda: Honoraria; Janssen: Honoraria, Research Funding; Genesis Pharma: Honoraria; GSK: Honoraria; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Matous: BeiGene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Eves: Zentalis: Current Employment, Current holder of stock options in a privately-held company; BMS: Ended employment in the past 24 months. Zheng: Zentalis Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Fiorino: Zentalis: Current Employment. Berdeja: Bristol Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Research Funding; Genentech: Research Funding; Sanofi: Consultancy, Research Funding; Bluebird bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Kite Pharma: Consultancy; Legend Biotech: Consultancy; SecuraBio: Consultancy; Takeda: Consultancy, Research Funding; Acetylon: Research Funding; Amgen: Research Funding; C4 Therapeutics: Research Funding; CARsgen: Research Funding; Cartesian Therapeutics: Research Funding; Celularity: Research Funding; EMD Sorono: Research Funding; Fate Therapeutics: Research Funding; GlaxoSmithKline: Research Funding; Ichnos Sciences: Research Funding; Incyte: Research Funding; Karyopharm: Research Funding; Lilly: Research Funding; Novartis: Research Funding; Poseida: Research Funding; Teva: Research Funding; Zentalis: Research Funding; 2Seventy bio: Research Funding.
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