In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 8057-8057
Abstract:
8057 Background: The recommended dose (RD) of SAR3419 administered intravenously every 3 weeks (q3w) for 6 cycles is 160 mg/m2 and is 55 mg/m2 when administered weekly (q1w) for 8-12 doses. Reversible corneal deposits were dose limiting (DLT) in the q3w schedule. The q1w schedule was well tolerated and active. However, based on the occurrence of late/cumulative adverse events (AE) at the RD supported by pharmacokinetic (PK) analyses showing ADC plasma accumulation after 4 weekly doses, an optimized schedule consisting of 4 weekly doses followed by 4 bi-weekly doses at the RD was tested. Methods: The q1w study was extended to treat 25 pts with the optimized schedule for 8 to 12 doses. Results: Twenty-one pts were evaluable. Main histologies were diffuse large B-cell (DLBCL) (9; 43%) and follicular (6; 29%). Median number of prior regimens was 2 [1-8], 6 pts received prior autologous transplantation and 95% of pts were Ann Arbor stage III-IV at study entry. Median number of doses received was 8 as planned with a median relative dose intensity of 1.0 [0.8-1.0] . Most frequent AEs were asthenia (1 pt with grade 3) and gastrointestinal disorders in 7 pts each. No AE fulfilled the defined DLT criteria. Reversible grade 1 blurred vision/corneal event occurred in 1 pt. Grade 3-4 haematological toxicities were minor consisting of non complicated neutropenia in 4 pts, thrombocytopenia in 2 pts and anemia in 1 pt with no transfusion support. Six (29%) pts, among them 3 with DLBCL, achieved an objective response including 3 CRu (1 in a pt refractory to last regimen). In addition, 9 (43%) pts had stable disease. Response duration was [8-35+] weeks, 5 pts still responding at the cut-off date. Conclusions: The optimized administration schedule shows an improved safety profile compared to prior tested schedules. The clinical efficacy is preserved essentially in aggressive lymphoma. The optimized schedule is being assessed in 2 phase II studies evaluating SAR3419 either as a single agent or in combination with rituximab in pts with DLBCL histology.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.8057
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
