Hematology Meeting Reports 2008;2(5):72-73 SESSION V M.S. Czuczman Update on galiximab: Roswell Park anti-CD80 monoclonal antibody Cancer Institute, Buffalo, NY, USA CD80 (B7.1) is a membrane- an excellent safety profile (i.e. bound co-stimulatory molecule similar to placebo). A phase I/II known for its role in regulating T- dose-escalation, single-agent, cell activity. Several studies sug- multiple dose study by Czuczman gest that it is also involved in the et al.3 demonstrated that 4 weekly regulation of normal and malig- infusions of galiximab were: well nant B-cells. CD80 is transiently tolerated and had modest anti- expressed on the surface of acti- tumor activity in relapsed/refrac- vated B-cells, antigen-presenting tory FL. A phase I/II study of gal- cells, and T-cells, but is constitu- iximab in combination with ritux- tively expressed on a variety of imab in relapsed/refractory FL by NHL’s (e.g. follicular lymphoma Leonard et al.4 has also been pub- (FL), Hodgkin’s lymphoma, etc.). lished. In this study, the overall Galiximab is a chimeric (“prima- response rate (ORR) at a galix- tized” = human IgG1 constant imab dose of 500 mg/m2 was 66% regions plus primate variable :19% CR, 14% CRu, and 33% regions) anti-CD80 monoclonal PR. Median PFS was 12.1 antibody (mAb) with low months. There appeared to be a immunogenicity. Cross-linking trend for patients in lower FLIPI CD80 with anti-CD80 on lym- risk groups and rituximab-naïve phoma cells in vitro has been patients to have better clinical shown to induce antibody- outcome as measured by ORR dependent cellular cytotoxicity and PFS. Based on these findings, (ADCC), upregulate proapoptotic an upfront, CALGB (50402) molecules, and inhibit cell prolif- phase II trial of “prolonged” dos- eration.1 Another possible mecha- ing of eight doses of combination nism of action may involve galiximab plus rituximab was per- immunomodulatory effects on formed and preliminary data host effector cells affecting the recently presented at the Lugano tumor microenvironment. In vivo, 2008 Lymphoma Meeting.5 galiximab delays tumor growth Primary objectives of CALGB and prolongs survival in a human 50402 were to determine the ORR lymphoma SCID mouse model.2 and time-to-progression after Based on its immunomodulatory upfront galiximab plus rituximab. properties, galiximab was initially Galiximab plus rituximab were studied at various doses/schedules given together weekly x 4; then as a treatment for plaque psoria- every 2 months x 4 in patients sis. These early studies demon- with previously untreated CD20- strated that galiximab could be positive FL patients: WHO grades safely infused over one hour with 1-3a; bulky Stage II or Stage | 72 | New Drugs in Hematology III/IV; measurable disease; adequate hemato- monotherapy study in relapsed Hodgkin’s lym- logic, hepatic and renal function; signed IRB- phoma; an in vivo mechanism-of-action pilot approved informed consent. Sixty-two patients study in FL to gain further insight into this were registered; one patient withdrew consent exciting novel mAb with multiple mecha- prior to initiating therapy. Base-line character- nisms-of-action, including direct antitumor, as istics of the 61 patients are: 61%M:39%F; well as possible immunomodulatory effects. median age = 57 years (range 22-85), with An update of available clinical data will be 48% of patients >60; 23% with an elevated presented at this meeting. LDH; FLIPI: good risk = 20.3%; intermediate- risk = 42%; high-risk =37%; histology = 44% grade 1; 46% grade 2; 10% grade 3a. An over- References all response rate of 69% (41% CR; 28% PR), 1. Suvas S, Singh V, Sahdev S, et al. Distinct role of CD80 with a 95% CI of (0.56, 0.80) was achieved. and CD86 in the regulation of the activation of B cell and B cell lymphoma. J Biol Chem 2002; 277:7766-75. Median F/U time is 1.4 years (range 0.3 to 2 2. Hariharan K, Anderson D, Leigh B, et al. Therapeutic years) and the estimated 1-year DFS probabil- activity of IDEC-114 (anti-CD80) and rituximab (Rituxan®) in B-cell lymphoma. Blood 2001;98:608a ity is 0.87 (0.75, 0.93). Treatment was very (abstract 2549). well tolerated, with only 13% experiencing 3. Czuczman MS, Thall A, Witzig TE, et al. Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or grade 3 AEs. Of interest, a subset of patients refractory follicular lymphoma. J Clin Oncol 2005; 23:4390-8. are demonstrating “delayed” tumor responses. 4. Leonard JP, Friedberg JW, Younes A, et al. A phase I/II Also, there appears to be a correlation between study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, responsiveness to galiximab plus rituximab follicular lymphoma. Annals of Oncology 2007;18:1216- therapy versus FLIPI score. Current galiximab 23. 5. Czuczman MS, Johnson JL, Jung SH, Cheson BD. A trials include: an international phase III, ran- phase II trial of extended induction ogaliximab ([G] andit-CD80 monoclonal antibody) plus rituximab [R] in domized, double-blind study comparing ritux- previously untreated follicular lymphoma (FL): Initial imab + placebo vs. rituximab + galiximab in report of CALGB study 50402. 10th International Conference on Malignant Lymphoma. Lugano, relapsed/refractory FL; a CALGB phase II Switzerland 2008. Hematology Meeting Reports 2008;2(5) | 73 | .