In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4034-4034
Abstract:
4034 Background: TGF-β2 overexpression in solid tumors triggers key cancer pathomechanisms, i.e. suppression of antitumor immune responses system and metastasis. Trabedersen specifically inhibits TGF-β2 expression. In the clinical Phase I/II study we evaluate MTD, safety, pharmakokinetics (PK), and efficacy of i.v. trabedersen in patients with advanced tumors. Methods: A total of 61 patients with pancreatic cancer (PancCa, n=37), malignant melanoma (MM, n=19), or colorectal carcinoma (n=5) were treated with i.v. trabedersen as 2 nd to 4 th -line therapy with escalating doses in 2 treatment schedules. (1 st schedule: 7d on, 7d off; 2 nd schedule: 4d on, 10d off; up to 10 cycles). Within the 1 st schedule, the MTD was established at 160 mg/m 2 /d. In the 2 nd schedule dose-escalation was stopped before reaching MTD. In the Phase II-part of the study further PancCa and MM patients were treated with 140 mg/m 2 /d. For assessment of PK parameters, plasma time profiles were analyzed for trabedersen and its n-1 to n-5 metabolites by non-compartimental analysis. Results: Trabedersen was safe and well-tolerated. The only expected adverse reaction identified is non-serious and transient thrombocytopenia. Only 2 SAEs (gastrointestinal hemorrhage und pyrexia) were considered as possibly related to study medication. Further clinical development will focus on PancCa patients receiving 140 mg/m 2 /d trabedersen as 2 nd -line treatment. Survival analysis of these patients revealed a mOS of 13.4 months (n=9; 95% CI: 2.2, 39.7). One PanCa patient had a complete response of liver metastases and is still alive after 75 months. Promising efficacy data were also seen in MM patients enrolled into the last cohort (140 mg/m 2 /day) with a current mOS of 9.3 months (n=14; 95% CI: 6.5, 12.2). PK analyses showed for both treatment schedules that exposure to trabedersen was in the expected range for all doses and half-life of trabedersen (1.12 to 2.08 hrs) as well as clearance (2.22-4.37 L/h*m 2 ) were independent of dose. Conclusions: Trabedersen showed excellent safety and encouraging survival results in the Phase I/II clinical study. A randomized, active-controlled study in 2 nd line stage IV PanCa patients is in preparation.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.4034
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
