Abstract
Early outcome results of a phase I/II study for an IL-2/T-cell receptor fusion protein in combination with gemcitabine and cisplatin (GC) in patients with locally advanced or metastatic urothelial cancer
Journal of clinical oncology, Vol.30(15_suppl), pp.e15010-e15010
05/20/2012
DOI: 10.1200/jco.2012.30.15_suppl.e15010
Abstract
e15010
Background: ALT-801 is a human IL-2/single-chain T-cell receptor fusion protein previously tested in a phase 1 in patients with advanced malignancy (Fishman 2011 CCR 17:7765) (CA097550). In various murine models, ALT-801 demonstrated potent activity against syngeneic and xenograft UC, suggesting sensitivity of this disease to IL-2 based immunotherapy (Wong, unpubl. data.). Although UC are sensitive to platinum-based chemotherapy, combinations such as gemcitabine (G) + cisplatin (C) are associated with CR rates of around 15%, and limited durability of responses with limited effects of retreatment. Methods: We report here initial efficacy results of co-administration of G (1000 mg/m
2
/dose, d 1 & 8), C (70 mg/m
2
/dose, d 1) and ALT-801 (escalating doses, d 3, 5, 8, 10) on a 21 day schedule, for 3 cycles, in patients with UC that was locally advanced, or metastatic, for whom GC chemotherapy would be considered. ALT-801 planned doses are 0.04 to 0.12 mg/kg/dose in 5 dose cohorts with a 3+3 escalation design. Subjects with at least stable disease after 3 courses may receive 4 additional weekly doses of ALT-801 alone. Results: To date, three Stage IV UC patients (1F, 2M; 59-63 yrs; 2 patients had predominantly nodal metastases and one patient liver metastases) completed treatment with 0.04 mg/kg ALT-801+GC. Two had previously undergone radical cystectomy and had then later failed following GC treatment. Grade 3/4 toxicities observed include neutropenia (2), thrombocytopenia (2), leukopenia (1), lymphopenia (1) and anemia (1), consistent with GC and ALT-801 known pharmacodynamic effects. All 3 had radiological CRs by week 13. One patient underwent radical cystectomy had a pCR. The next (0.06 mg/kg/dose) cohort has started treatment. A phase II expansion cohort is planned at the MTD. Conclusions: The early response pattern is encouraging in that ALT-801 may be a novel, active immunotherapy for UC. NCT01326871
Details
- Title: Subtitle
- Early outcome results of a phase I/II study for an IL-2/T-cell receptor fusion protein in combination with gemcitabine and cisplatin (GC) in patients with locally advanced or metastatic urothelial cancer
- Creators
- Julio Hajdenberg - M.D. Anderson Cancer Center Orlando, Orlando, FLDanny Landau - M.D. Anderson Cancer Center Orlando, Orlando, FLDaniel A. Vaena - University of IowaMayer N. Fishman - Moffitt Cancer CenterCharles Joel Rosser - M.D. Anderson Cancer Center Orlando, Orlando, FLMohammed M. Milhem - University of IowaJeffrey S. Weber - Moffitt Cancer CenterVirginia Rizzo - M.D. Anderson Cancer Center Orlando, Orlando, FLPamela Zehr - University of IowaIrene Williams-Elson - Moffitt Cancer CenterPeter Rhode - Altor BioScienceTessa Schutt - Altor BioScienceLiza Hernandez - Altor BioScienceBee-Yau Huang - Altor BioScienceHing C. Wong - Altor BioScience
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.30(15_suppl), pp.e15010-e15010
- DOI
- 10.1200/jco.2012.30.15_suppl.e15010
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363306702771
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