Abstract
2611 Background: Trabedersen (AP 12009) is a TGF-β2-specific antisense oligonucleotide. In a randomized and active-controlled phase IIb study in high-grade glioma patients, a clear survival benefit for trabedersen treatment over standard chemotherapy was found. In this study we evaluate the maximum tolerated dose (MTD), safety, pharmakokinetics, and efficacy of intravenous treatment with trabedersen in patients (pts) with other advanced solid tumors. Methods: In the open label, multicenter, dose-escalation phase I/II study, 33 pts with advanced pancreatic carcinoma (PancCa, stage IVA/IVB, N=23), malignant melanoma (stage III/IV, N=5), or colorectal carcinoma (stage III/IV, N=5) were enrolled in several cohorts. Pts were treated intravenously with trabedersen as 2nd to 4th-line therapy as monotherapy with escalating doses in 2 treatment schedules (1st schedule: 7d on, 7d off; 2nd schedule: 4d on, 10d off; up to 10 cycles). Results: Trabedersen showed high safety and tolerability. The only expected adverse reaction identified was nonserious, transient thrombocytopenia. Within the 1st schedule, MTD was established at 160 mg/m2/d. In the 2nd schedule dose escalation was stopped after the 4th cohort without reaching a MTD, as a well tolerated dose (140 mg/m2/d) with promising efficacy was identified. The median overall survival for pts with advanced PancCa treated with this dose (N=5) was 13.4 months. Further promising efficacy data include the following: a PancCa patient had a complete, sustained response of liver metastasis and is alive 49 months after enrollment; a melanoma patient survived 13.8 months, one melanoma patient is still alive after 12.8 months. Conclusions: Currently the study continues with the treatment of 24 pts with pancreatic carcinoma or malignant melanoma with a dose of 140 mg/m2/d. A randomized, active-controlled study is in preparation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisense Pharma GmbH
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