Abstract
Clinical experience of a targeted TCR-IL2 fusion protein in combination with cisplatin (CDDP) in patients (pts) with metastatic melanoma
Journal of clinical oncology, Vol.30(15_suppl), pp.e13088-e13088
05/20/2012
DOI: 10.1200/jco.2012.30.15_suppl.e13088
Abstract
e13088
Background: ALT-801 is recombinant human interleukin-2 (IL-2) genetically fused to a single-chain T-cell receptor specific to a peptide antigen of human p53 presented in the context of HLA-A2 positivity. In melanoma xenograft mouse models, this fusion protein alone demonstrated potent, targeted antitumor activity and synergistic efficacy was observed in combination with CDDP. A prior phase I study in pts with metastatic malignancies, including metastatic melanoma, showed that ALT-801 monotherapy could be safely administered and was associated with immunologic changes of potential antitumor relevance (Fishman 2011 CCR 17:7765). Here we report the results of a phase Ib study of ALT-801+ CDDP in pts with metastatic melanoma. Methods: The primary objectives of this multicenter study are to: 1) define an MTD and evaluate the safety of ALT-801+CDDP and 2) assess the objective response rate according to RECIST criteria in treated patients. Eligible pts (histologically confirmed advanced/metastatic melanoma, p53 peptide/HLA-A2
+
tumor, chemotherapy naive, PS (ECOG) 0-1, adequate renal and cardiac functions) received 2 consecutive 4-wk courses of CDDP (70 mg/m
2
iv, Day 1) and ALT-801 (iv, Days 3, 5, 15, 17 & 19). Pts with SD or better after 2 courses received 2 additional courses of treatment. Up to 5 cohorts (3+3 dose escalation) of ALT-801 (0.04 - 0.12 mg/kg) were planned with a 2-stage design of expanded pt enrollment at the MTD. Results: 22 patients (11M, 11F, 30-74 yrs) were evaluable at ALT-801 dose levels from 0.04 to 0.10 mg/kg. The MTD has not been reached at 0.10 mg/kg ALT-801. Toxicity was manageable and transient. RECIST-confirmed tumor response and disease stabilization was reported for some patients. Overall survival rates (6 mon, 87%; 12 mon, 58%) observed to date suggest durable clinical benefit. Conclusions: ALT-801+CDDP can be safely administered in an out-patient setting to pts with metastatic melanoma. Preliminary evaluation suggests durable clinical activity of the ALT-801+CDDP regimen in melanoma patients. A trial using ALT-801 at the 0.1 mg/kg dose level in combination with a BRAF kinase inhibitor is being planned for patients with metastatic melanoma (CA097550).
Details
- Title: Subtitle
- Clinical experience of a targeted TCR-IL2 fusion protein in combination with cisplatin (CDDP) in patients (pts) with metastatic melanoma
- Creators
- Mohammed M. Milhem - University of IowaJeffrey S. Weber - Moffitt Cancer CenterAsim Amin - Carolinas Medical CenterSanjiv S Agarwala - St. Luke's HospitalDavid H. Lawson - Emory UniversityJohn A. Thompson - Seattle Cancer Care AllianceSteven O'Day - Angeles Clinic and Research InstituteGregory K. Pennock - M. D. Anderson Cancer Center Orlando, Orlando, FLJon M. Richards - Oncology SpecialistsTimothy Kuzel - Northwestern UniversityLiza Hernandez - Altor BioScience (United States)Bee-Yau Huang - Altor BioScience (United States)Peter Rhode - Altor BioScience (United States)Hing C. Wong - Altor BioScience (United States)
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.30(15_suppl), pp.e13088-e13088
- DOI
- 10.1200/jco.2012.30.15_suppl.e13088
- 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
- 9984363178202771
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