Indatuximab Ravtansine (BT062) in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma: Clinical Activity in Patients Already Exposed to Lenalidomide and Bortezomib

摘要: Background: BT062 (Biotest AG Dreieich, Germany) is an antibody-drug conjugate (ADC), comprising the anti-CD138 chimerized MAb (nBT062) and maytansinoid DM4 as a cytotoxic agent. It designed to bind CD138 on cancer cells, then release after internalization cause cell death. (Syndecan-1) highly overexpressed various solid tumors in hematological malignancies, represents one of most specific target antigens for identification multiple myeloma (MM) cells. was investigated single agent found have acceptable tolerability profile evidence activity patients with heavily pretreated relapsed and/or refractory MM (1). Preclinical studies showed enhanced anti-MM when combined lenalidomide dexamethasone (Len/Dex). Based these data, Phase I/IIa study initiated evaluate safety efficacy combination Len/Dex. Objectives: To determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase II (RPTD), pharmacokinetics (PK), increasing doses (days 1, 8, 15, every 4 weeks) used Len (25 mg, daily days 1-21) low Dex (40 mg 22) MM. Methods: This prospective, open label, multicenter study. The I part includes escalation, IIa expansion RPTD cohort. Patients aged ≥18 years who failed at least prior therapy were eligible participate. Prior treatment allowed. clinical response (or no progressive disease) without unacceptable additional cycles. enrolled cohorts 3 each level; DLT first cycle triggered cohort expansion. Toxicities assessed by CTCAE v4 according International Myeloma Working Group criteria. Results: administered (MAD) 120 mg/m². Two six treated this had DLT: mucosal inflammation (CTC grade 3) anemia 3). MTD defined 100 mg/m² selected RPTD. Additional are being further efficacy. Enrollment into ongoing. As July 2014, total 45 received levels 80 (N=3), (N=36) or (N=6). Fifteen discontinued treatment: 5 disease progression, 7 adverse events, 1 died (not related) 2 withdrawal consent. other 30 remain treatment. median duration 123 (range 1–597). number therapies 1–11). 68% exposure both bortezomib, 73% exposure, 30% Len-refractory. According preliminary data from ongoing study, about 89% reported Adverse Events (AEs) CTC 2. common AEs diarrhea, fatigue, nausea, hypokalemia. Amongst 36 across all currently evaluable efficacy, overall rate (ORR) 78%; including stringent complete response, responses, 10 very good partial 15 responses. achieved minor 6 stabilization, resulting benefit 100% patients. ORR 83% among receiving Interestingly, 70% 23 Len. Conclusion: Preliminary indicate that well Len/Dex induce responses myeloma, bortezomib Updated results will be presented. References 1. Heffner et al , BT062, Antibody-Drug Conjugate Directed Against CD138, Given Weekly Weeks Each Week Cycle: Safety Further Evidence Clinical Activity. Blood. 2012; 120: Abstract 4042. Disclosures Kelly: Celgene: Speakers Bureau. Heffner: Amgen: Honoraria, Research Funding; Biotest: Dana Farber CI: Genentech: Gilead: Idera: Janssen: Pfizer: Pharmacyclics: Onyx: Spectrum: Talon Therapeutics: Funding. Somlo: Millennium: Membership entity's Board Directors advisory committees, Bureau; Novartis: committees; committees. Siegel: Munshi: Consultancy; Sanofi-Aventis: Ocopep: Consultancy, Equity Ownership, Patents & Royalties. Jagannath: Sanofi: Consultancy. Lonial: BMS: Ailawadhi: Honoraria. Barmaki-Rad: Biotest AG: Employment. Chavan: Pharmaceuticals: Patel: Wartenberg-Demand: Haeder: Anderson: Sanofi Aventis: Oncopep: Ownership; Acetylon: Ownership.