24.12.2012 Views

Annual Meeting Proceedings Part 1 - American Society of Clinical ...

Annual Meeting Proceedings Part 1 - American Society of Clinical ...

Annual Meeting Proceedings Part 1 - American Society of Clinical ...

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

TPS8110 General Poster Session (Board #40C), Mon, 1:15 PM-5:15 PM<br />

Phase III study <strong>of</strong> investigational MLN8237 (alisertib) versus investigator’s<br />

choice in patients (pts) with relapsed/refractory (rel/ref) peripheral T-cell<br />

lymphoma (PTCL). Presenting Author: Owen O’Connor, Center for Lymphoid<br />

Malignancies, Columbia University Medical Center, New York, NY<br />

Background: PTCL is a rare form <strong>of</strong> aggressive non-Hodgkin lymphoma<br />

(NHL), accounting for 5–20% <strong>of</strong> NHL diagnoses. Standard NHL therapies<br />

developed primarily for B-cell lymphomas are not optimal for PTCL and<br />

early relapse is common. Current treatments for rel/ref PTCL include<br />

pralatrexate, romidepsin, and gemcitabine; however, outcomes remain<br />

poor. The oral, investigational drug, MLN8237, is a selective inhibitor <strong>of</strong><br />

Aurora A kinase (AAK) – a key mitotic regulator that is overexpressed or<br />

amplified in various human tumors. Emerging clinical data from a phase II<br />

study <strong>of</strong> single agent MLN8237 in rel/ref aggressive T-cell lymphoma<br />

(Friedberg et al, ASH 2011) support further clinical evaluation in this<br />

indication. Methods: In this open-label, randomized, phase III study, a<br />

maximum <strong>of</strong> 354 adults with rel/ref PTCL after �1 prior systemic cytotoxic<br />

therapies will be enrolled at approximately 140 centers worldwide. Pts will<br />

be randomized 1:1 to MLN8237 50 mg twice daily as an enteric coated<br />

tablet on days 1–7 <strong>of</strong> 21-day cycles, or to investigator’s choice <strong>of</strong>:<br />

pralatrexate 30 mg/m2 IV once weekly for 6 weeks in 7-week cycles;<br />

romidepsin 14 mg/m2 IV on days 1, 8, and 15 <strong>of</strong> 28-day cycles; or<br />

gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 <strong>of</strong> 28-day cycles. Pts<br />

with disease response/stabilization will be able to continue treatment<br />

provided that clinical benefit is demonstrated and treatment is tolerable.<br />

The expected study duration is 44 months. Primary endpoints are overall<br />

response rate (complete response [CR] � partial response) and progression<br />

free survival by International Working Group criteria (Cheson et al, 2007).<br />

Secondary endpoints include CR rate, overall survival, time to progression,<br />

time to response, duration <strong>of</strong> response, safety, and quality <strong>of</strong> life.<br />

Exploratory endpoints include an evaluation <strong>of</strong> candidate biomarkers (such<br />

as AAK protein expression levels and gene amplification, and the tumor<br />

proliferative marker Ki-67) in tumor biopsies. This study is registered at<br />

<strong>Clinical</strong>Trials.gov: #NCT01482962.<br />

TPS8112 General Poster Session (Board #40E), Mon, 1:15 PM-5:15 PM<br />

ELOQUENT-2: A phase III, randomized, open-label trial <strong>of</strong> lenalidomide/<br />

dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or<br />

refractory multiple myeloma (RR MM) (CA204-004). Presenting Author:<br />

Sagar Lonial, Multiple Myeloma Research Consortium, Norwalk, CT/<br />

Winship Cancer Institute <strong>of</strong> Emory University, Atlanta, GA<br />

Background: MM remains incurable and patients (pts) typically relapse or<br />

become refractory to current treatments. Novel regimens are needed to<br />

improve pt outcomes. Elo is a humanized monoclonal IgG1 antibody<br />

targeting the cell surface glycoprotein CS1, which is highly expressed on<br />

�95% <strong>of</strong> MM cells. Len/Dex is approved for treatment <strong>of</strong> relapsed MM and<br />

an objective response rate (ORR) <strong>of</strong> ~60% was reported in phase III trials <strong>of</strong><br />

this combination in RR MM. In a phase II study (N�73) <strong>of</strong> Elo (10 or 20<br />

mg/kg) in combination with Len/Dex in pts with RR MM, the 10 mg/kg<br />

group (n�36) demonstrated an ORR <strong>of</strong> 92% and median progression-free<br />

survival (PFS) that was not reached after a median follow-up <strong>of</strong> 14.1<br />

months. Encouraging activity was seen in patients with high-risk cytogenetics<br />

and/or stage 2-3 disease. Based on these data, a randomized,<br />

open-label phase III trial has been initiated to determine if the addition <strong>of</strong><br />

Elo to Len/Dex will improve PFS in patients with RR MM compared with<br />

Len/Dex alone. Methods: Pts (N�640) with RR MM and 1-3 prior therapies<br />

are eligible, including pts with mild or moderate renal impairment. Pts are<br />

randomized in a 1:1 ratio to receive 28-day cycles <strong>of</strong> Len 25 mg PO (days<br />

1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo<br />

dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles<br />

and on days 1 and 15 in subsequent cycles. Dex 8 mg IV � 28 mg PO is<br />

used during the weeks with Elo. Treatment will continue until disease<br />

progression, death, or withdrawal <strong>of</strong> consent. Patients will be followed for<br />

tumor response every 4 weeks until progressive disease and then survival<br />

every 12 weeks. The primary endpoint is PFS (90% power for a hazard ratio<br />

[experimental to control arm] <strong>of</strong> 0.74) and the secondary endpoints are<br />

ORR and overall survival. Exploratory endpoints are safety, time to<br />

response, duration <strong>of</strong> response, time to subsequent therapy, health-related<br />

quality <strong>of</strong> life, and pharmacokinetics and immunogenicity <strong>of</strong> Elo. Potential<br />

biomarkers will also be assessed. As <strong>of</strong> January 10th, 2012, 107 pts were<br />

enrolled and 68 pts were treated. NCT01239797.<br />

Lymphoma and Plasma Cell Disorders<br />

537s<br />

TPS8111 General Poster Session (Board #40D), Mon, 1:15 PM-5:15 PM<br />

Pilot study <strong>of</strong> MAGE-A3 protein vaccination and autologous stem cell<br />

transplantation (autoSCT) as consolidation therapy for multiple myeloma<br />

(MM). Presenting Author: Adam D. Cohen, Fox Chase Cancer Center,<br />

Philadelphia, PA<br />

Background: MAGE-A3 is a cancer-testis antigen (CT Ag) commonly<br />

expressed in MM but not in normal non-gonadal tissues. MAGE-A3<br />

inhibited p53-dependent and independent apoptosis in MM cells (Clin<br />

Cancer Res 2011;17:4309), and spontaneous immunity against CT Ags in<br />

MM patients was associated with favorable clinical outcomes (Blood<br />

2007;109:1103; Blood 2008;112:3362), making it a rational target for<br />

immunotherapy. In this study (NCT01380145), we are examining if a<br />

recombinant (rec) MAGE-A3 protein vaccine � adjuvant combined with<br />

vaccine-primed peripheral blood lymphocytes (PBL) can safely stimulate<br />

antigen-specific immunity in MM patients undergoing autoSCT for consolidation<br />

therapy. Methods: Patients meeting the following criteria are<br />

eligible: within 12 months <strong>of</strong> diagnosis; MAGE-A� MM cells by immunohistochemistry;<br />

achieving at least a very good partial response with induction<br />

therapy; and meeting institutional criteria for autoSCT. One patient <strong>of</strong> a<br />

planned cohort <strong>of</strong> sixteen has been enrolled. Six weeks before SCT,<br />

subjects will receive their first vaccination (300 �g IM) and three weeks<br />

later undergo leukopheresis to collect vaccine-primed PBL. They then<br />

undergo stem cell mobilization followed by a standard melphalanconditioned<br />

autoSCT. On day 3 after stem cell infusion, the unmanipulated,<br />

primed PBL will be re-infused followed by the second recMAGE-A3<br />

vaccination on day 10. An additional six vaccinations will be administered<br />

on days 31, 52, 73, 94, 180, and 270 after autoSCT. The primary<br />

objectives are safety and tolerability. The secondary objectives <strong>of</strong> cellular<br />

and humoral immune responses and lymphocyte reconstitution will be<br />

assessed by a validated series <strong>of</strong> quantitative assays using established<br />

response criteria (PNAS 2008;105:1650). Success criteria based on<br />

immune response have not been specified for this pilot study, though<br />

induction <strong>of</strong> MAGE-A3 immunity in at least 50% <strong>of</strong> patients would merit<br />

consideration for further evaluation <strong>of</strong> clinical efficacy.<br />

TPS8113 General Poster Session (Board #40F), Mon, 1:15 PM-5:15 PM<br />

ELOQUENT-1: A phase III, randomized, open-label trial <strong>of</strong> lenalidomide/<br />

dexamethasone with or without elotuzumab in subjects with previously<br />

untreated multiple myeloma (CA204-006). Presenting Author: Meletios A.<br />

Dimopoulos, Hellenic Cooperative Oncology Group, Athens, Greece<br />

Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody<br />

targeting the cell surface glycoprotein CS1, which is highly expressed on<br />

�95% <strong>of</strong> MM cells. In a MM xenograft mouse model, the combination <strong>of</strong><br />

Elo � lenalidomide (Len) significantly reduced tumor volume in a synergistic<br />

manner compared with either agent alone. In a phase 2 study (N�73) <strong>of</strong><br />

Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone<br />

(Dex) in pts with RR MM, the 10 mg/kg dose group (n�36)<br />

demonstrated objective response rates (ORR) <strong>of</strong> 92% in all pts, and 100%<br />

in pts who had received only 1 prior therapy (n�16). The higher response<br />

rate in pts with fewer prior lines <strong>of</strong> therapy provides a rationale for<br />

investigating this combination earlier in the disease course. This randomized,<br />

open-label, phase 3 trial will determine if the addition <strong>of</strong> Elo to<br />

Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed,<br />

untreated MM. Methods: Pts (N�750) with newly diagnosed<br />

symptomatic MM ineligible for stem cell transplant will be randomized in a<br />

1:1 ratio to receive 28-day cycles <strong>of</strong> Len 25 mg PO (days1-21) and Dex 40<br />

mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is<br />

10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15<br />

<strong>of</strong> cycles 3-18 followed by 20 mg/kg on day 1 <strong>of</strong> cycle 19 onward. Dex 8 mg<br />

IV � 28 mg PO is used during the weeks with Elo. Treatment will continue<br />

until disease progression, death, or withdrawal <strong>of</strong> consent. Pts will be<br />

followed up for response every 4 weeks until progressive disease and for<br />

survival every 16 weeks. The primary endpoint is PFS (90% power for a<br />

hazard ratio [experimental to control arm] <strong>of</strong> 0.74) and the secondary<br />

endpoints are ORR and overall survival. Exploratory endpoints are safety,<br />

time to response, duration <strong>of</strong> response, time to subsequent therapy,<br />

health-related quality <strong>of</strong> life, and pharmacokinetics and immunogenicity <strong>of</strong><br />

Elo. Potential biomarkers will also be assessed. As <strong>of</strong> January 1, 2012, 13<br />

pts were enrolled and 9 pts were treated. NCT01335399.<br />

Visit abstract.asco.org and search by abstract for the full list <strong>of</strong> abstract authors and their disclosure information.

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!