Update on vantage program to assess combined vorinostat (V) and bortezomib (B) in patients (pts) with relapsed and/or refractory (RR) multiple myeloma (MM).

8133^ Background: Preclinical data show combined histone deacetylase (HDAC) and proteasome inhibition may have synergistic cytotoxicity in MM cells. In RR MM pts, V (oral HDAC inhibitor) plus B showed objective response rates (ORR; ≥PR) up to 42% in all pts, including B refractory in 2 Phase I trials. These preliminary data provided rationale for a large global program in RR MM (∼900 pts) to assess the efficacy/safety of combined V and B for the treatment of RR MM (2 trials). Methods: Vantage 088 (088) is a Phase III, randomized, double-blind study of V or placebo (P) plus B in MM pts with progressive disease after 1-3 prior anti-myeloma treatments. Primary endpoint (EP) is progression-free survival (PFS) with planned accrual of 742 pts. Vantage 095 (095) is a Phase IIb open-label study of V plus B in RR MM pts after ≥2 prior anti-myeloma therapies. All 095 pts are refractory to B and relapsed, refractory, intolerant, or ineligible for other MM therapies. Primary EP is ORR (≥PR) with planned accrual of 142 pts. In both, pts received iv B 1.3 mg/m2 on Days 1, 4, 8, and 11 and oral V 400 mg (or matching P in 088) qd on Days 1-14 of each 21-day cycle. Results: As of Dec 2009, 140 and 65 pts, respectively, were enrolled in 088 and 095. In both, >40% have completed ≥3 cycles. Safety data from pts who received study drug (088, n = 39; 095, n = 30) were the earliest data evaluated by the independent data monitoring committee (DMC; cut-off Aug 2009). Grade ≥3 drug-related AEs seen in 9 pts in 088 (thrombocytopenia, 5 pts; nausea/vomiting, 2 pts) and 19 pts in 095 (most commonly thrombocytopenia, 8 pts; nausea, 5 pts); higher frequency of toxicities was expected in 095 due to population differences. DMC did not recommend study stop/change based on safety. Safety and efficacy data from interim analyses (IA) of the unblinded study will be reported; first formal IA (with futility/efficacy stopping rules) for 088 is planned when 25% (126 events) of PFS events seen, and IA from 095 was conducted after evaluation of ≥43 pts, where the defined futility threshold was surpassed. Conclusions: Combined V and B is being investigated in 2 global, multicenter trials in RR MM pts to determine if the regimen is a viable option for RR MM pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Genomic Health, sanofi-aventis Amgen, Genomic Health, sanofi-aventis In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.