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  • 1
    Online Resource
    Online Resource
    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.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e15010-e15010
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e15010-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
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e15010
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Online Resource
    Phase I/II clinical trial of ALT-801, a T-cell receptor/IL-2 fusion protein, plus gemcitabine and cisplatin in urothelial cancer.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 6_suppl ( 2013-02-20), p. 271-271
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 271-271
    Abstract: 271 Background: ALT-801, a T-cell receptor/IL-2 fusion protein, activates NK and CD4 + lymphocytes to secrete IFN-gamma which re-polarizes tumor associated macrophages from M1 to M2 in various murine tumor models. CD8 + memory cells also acquire an innate immune phenotype and become expanded upon ALT-801 activation. Via this novel mechanism, ALT-801 mounted effective immune responses and maintained immunological memory against urothelial cancer in these models. Pretreatment chemotherapy eliminated myeloid-derived suppressive cells, potentiating the anti-tumor effects of ALT-801 (Wong, unpublished data). Previous clinical studies with ALT-801 (advanced malignancy; Fishman 2011 CCR 17:7765) and ALT-801 + cisplatin (melanoma; NCT01029873) showed anti-tumor activity in these settings. Methods: We evaluated co-administration of gemcitabine [G] (1000 mg/m 2 /dose, day 1 and 8) and cisplatin [C] (70 mg/m 2 /dose, day 1) with ALT-801 (escalating doses; days 3, 5, 8, 10) for three 21-day cycles, in patients with metastatic urothelial cancer. Those with at least stable disease after 3 courses could receive 4 additional weekly doses of ALT-801 alone. ALT-801 doses were planned at 0.04 to 0.12 mg/kg/dose in 5 cohorts with a 3+3 escalation design. Results: The dose-escalation is completed, with a recommended dose of ALT-801 of 0.06 mg/kg/dose. The best objective response rate (ORR, RECIST v1.1) among 5 chemo-naïve subjects was 100% (2 CR, 3 PR) and among 5 previously treated patients 60% (1 CR, 2 PR), for an overall total of 80% (3 CR, 5 PR, 1 SD, 1 PD). One of 2 patients who underwent radical cystectomy was confirmed pathologically free of tumor. Responding lesions included bulky and extensive liver and pulmonary metastases, and adenopathy. ALT-801 at the 0.06 mg/kg/dose level in this combination was adequately-tolerated. Grade 3/4 toxicities including neutropenia, thrombocytopenia and lymphopenia, appear consistent with known G, C, and ALT-801 effects. Conclusions: ALT-801 is a novel and potentially active immunotherapy for urothelial cancer. More patients are in treatment on the open phase 2 expansion portion of the study (NCT01326871), and updated interim results are anticipated (CA097550). Clinical trial information: NCT01326871.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.6_suppl.271
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
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