RATIONALE: Diagnostic procedures, such as radionuclide imaging using bispecific antibody, may help find colorectal cancer cells and learn the extent of disease.
PURPOSE: This phase I trial is studying how well a bispecific antibody works in finding tumor cells in patients with colorectal cancer.

开始日期2008-11-01

申办/合作机构

Garden State Cancer Center

NCT00006458 / Unknown status临床1期IIT

Phase I Non-Myeloablative Trial With 90Y-Humanized MN-14 (Anti-CEA) Antibody for Relapsed or Refractory Advanced Non-Small Cell Lung Cancer (NSCLC)

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients who have relapsed or refractory non-small cell lung cancer.

开始日期2000-08-01

申办/合作机构

Garden State Cancer Center

[+1]

NCT00006347 / Unknown status临床1期IIT

Phase I Non-Myeloablative Trial With 90Y-Humanized MN-14 (Anti-CEA) Antibody for Relapsed or Refractory Small Cell Lung Cancer (SCLC)

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have relapsed or refractory small cell lung cancer.

开始日期2000-08-01

申办/合作机构

Garden State Cancer Center

[+1]

100 项与 Garden State Cancer Center 相关的临床结果

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0 项与 Garden State Cancer Center 相关的专利（医药）

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171

项与 Garden State Cancer Center 相关的文献（医药）

2014-11-01·Molecular Cancer Research

Abstract A07: Phase I evaluation of anti-human leukocyte antigen-DR monoclonal antibody therapy in spontaneous canine lymphoma

作者: Page, Rodney ; Biller, Barbara J. ; Sharkey, Robert ; Goldenberg, David M.

AbstractIMMU-114 (also known as hL243) is a humanized anti-HLA-DR monoclonal antibody (mAb) with potent anti-tumor activity against a broad range of human hematopoietic malignancies. As MHC Class II antigens are also expressed on canine lymphocytes, IMMU-114 has previously been found to recognize and kill malignant lymphocytes collected from dogs with spontaneous B cell lymphoma. Canine lymphoma is a highly relevant animal model of B-cell non-Hodgkin's lymphoma (NHL) in humans with many advantages over rodent models. In addition, clinical trials in pet dogs can be designed to address therapeutic endpoints relevant to phase II/III studies in both dogs and humans.This study is being undertaken to determine the safety, pharmacodynamic and pharmacokinetic profiles of IMMU-114 in dogs with heavily pre-treated B cell lymphoma (NHL). Our hypothesis is that the mAb can safely be administered to tumor-bearing dogs and that it will be preferentially cytotoxic to B lymphocytes. Our overall objectives are to characterize the toxicity and biologic profile of IMMU-114 to advance the therapy of canine lymphoma and to better inform human clinical trials using anti-HLA-DR mAbs.Thirteen pet dogs with B cell lymphoma demonstrating binding to IMMU-114 have been enrolled in an on-going phase I clinical trial at the Flint Animal Cancer Center at Colorado State University. Enrollment follows a standard 3 x 3 dose escalation to identify the maximally tolerated dose (MTD) of the mAb, starting at a dose of 3 mg/kg, and escalating thus far to 6, 12, and 24 mg/kg. Data collection includes pre and post-infusion peripheral blood mononuclear cells (PBMCs), serum, serial lymph node measurements, complete blood counts and serum chemistry profiles. Preliminary pharmacodynamic evaluation shows a significant and transient dose-dependent decrease in the percentage and absolute number of B lymphocytes in the blood of treated dogs 24 hours post infusion. This corresponds to a transient increase in the relative percentage of T lymphocytes. Neutropenia and other bone marrow toxicities have not been observed. Infusion related side effects appear common but have been mild to moderate in nature with 10/13 patients experiencing grade 1 or grade 2 allergic reactions (fever, urticaria, and hypersalivation) and 2/13 with grade 1 nausea. No dose limiting toxicities have been observed; therefore the MTD has not yet been reached. Thus far 2/13 dogs (15%) have had prolonged disease stabilization and received multiple weekly infusions of 12 mg/kg while 11/13 dogs have had progressive disease (lymph node enlargement) within one week post therapy. Pharmacokinetic data obtained at the end of infusion, 2, 24 hours and 1 and 2 weeks post infusion showed minimally detectable levels at doses of 3 and 6 mg/kg. At 12 mg/kg, 2 animals had evidence of persistent antibody levels in serum for 24 hours, followed by return to pre-treatment levels within 6 days. Two dogs currently treated at 24 mg/kg maintained hL243 levels in their blood over 1 day, with residual antibody still found in the blood 6 days later Four of the 13 dogs developed anti-hL243 responses 2 to 4 weeks after treatment initiation. These findings provide a rationale for larger clinical studies to investigate the efficacy of anti-HLA-DR mAbs for both veterinary and human applications.Citation Format: Barbara J. Biller, Rodney Page, Robert Sharkey, David M. Goldenberg. Phase I evaluation of anti-human leukocyte antigen-DR monoclonal antibody therapy in spontaneous canine lymphoma. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A07.

2014-10-01·Cancer Research

Abstract CT211: IMMU-130, an SN-38 antibody-drug conjugate (ADC) targeting CEACAM5, is therapeutically active in metastatic colorectal cancer (mCRC): Initial clinical results of two Phase I studies

作者: Segal, Neil H. ; Wegener, William A. ; Saltz, Leonard B. ; Govindan, Serengulam V. ; Berlin, Jordan D. ; Goldenberg, David M. ; Dotan, Efrat ; Maliakal, Pius P. ; Sharkey, Robert M. ; Starodub, Alexander N. ; Guarino, Michael J.

AbstractIMMU-130, an ADC of the active metabolite of CPT-11, SN-38, conjugated by a pH-sensitive linker (7.6 average drug-antibody ratio) to the humanized anti-CEACAM5 antibody (labetuzumab), is completing two Phase I trials. In both, eligible patients with advanced mCRC were required to have failed/relapsed standard treatments, one being the topoisomerase-I inhibiting drug, CPT-11 (irinotecan), and an elevated plasma CEA (>5 ng/mL). IMMU-130 was administered every 14 days (EOW) at doses starting from 2.0 mg/kg in the first protocol (IMMU-130-01). Febrile neutropenia occurred in 2 of 3 patients at 24 mg/kg; otherwise at ≤16 mg/kg, neutropenia (≥ Grade 2) was observed in 7 patients, with one also experiencing thrombocytopenia. One patient [of 8 who received > 4 doses (2 cycles)] showed a 40.6% decrease in liver (starting at 7 cm) and lung target lesions (PR by RECIST) for 4.7 months, with no major toxicity, tolerating a total of 18 doses at 16 mg/kg. The study is continuing at 12 mg/kg EOW. Since SN-38 is most effective in S-phase cells, a more protracted exposure could improve efficacy. Thus, in a second Phase I trial (IMMU-130-02), dosing was intensified to twice-weekly, starting at 6 mg/kg/dose for 2 weeks (4 doses) with 1 week off, as a treatment cycle, in a 3+3 trial design. Neutropenia and manageable diarrhea were the major side effects, until dose reduction to 4.0 mg/kg twice-weekly, with early results indicating multiple cycles are well-tolerated. Currently, tumor shrinkage occurred in 3 patients, with 1 in continuing PR (-46%) by RECIST, among 6 patients who completed >4 doses (1 cycle). In both trials, CEA blood titers correlated with tumor response, and high levels did not interfere with therapy. There have been no anti-antibody or anti-SN-38 antibody reactions, based on ELISA tests. In each study, the ADC was cleared by 50% within the first 24 h, which is much longer exposure than with typical doses of the parental molecule, CPT-11. These results indicate that this novel ADC, given in different regimens averaging ∼16-24 mg/kg/cycle, shows therapeutic activity in advanced mCRC patients. Since CEACAM5 has elevated expression in breast and lung cancers, as well as other epithelial tumors, it may be a useful target in other cancers as well. A Phase II trial evaluating twice-weekly dosing and a new regimen, once-weekly x 2 every 21 days, is ongoing in mCRC.Citation Format: Neil H. Segal, Efrat Dotan, Jordan D. Berlin, Alexander N. Starodub, Michael J. Guarino, Leonard B. Saltz, Pius P. Maliakal, Serengulam V. Govindan, William A. Wegener, Robert M. Sharkey, David M. Goldenberg. IMMU-130, an SN-38 antibody-drug conjugate (ADC) targeting CEACAM5, is therapeutically active in metastatic colorectal cancer (mCRC): Initial clinical results of two Phase I studies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT211. doi:10.1158/1538-7445.AM2014-CT211

2014-10-01·Cancer Research

Abstract CT206: SN-38 antibody-drug conjugate (ADC) targeting Trop-2, IMMU-132, as a novel platform for the therapy of diverse metastatic solid cancers: Initial clinical results

作者: Ocean, Allyson J. ; Shah, Manish A. ; Maliakal, Pius P. ; Vahdat, Linda T. ; Thomas, Sajeve S. ; Goldenberg, David M. ; Chuang, Ellen ; Starodub, Alexander N. ; Wegener, William A. ; Picozzi, Vincent J. ; Govindan, Serengulam V. ; Guarino, Michael J. ; Sharkey, Robert M.

AbstractIMMU-132 is an ADC of the active metabolite of CPT-11, SN-38, conjugated by a pH-sensitive linker (average drug-antibody ratio = 7.6) to the humanized anti-Trop-2 antibody, hRS7, exhibiting rapid internalization after binding to Trop-2. Trop-2 is a type I transmembrane protein expressed at high prevalence (∼1 x 10*5) and specificity by many carcinomas. We report the results of a Phase I clinical trial of 25 patients with different metastatic cancers (pancreatic, 7; triple-negative breast [TNBC], 4; colorectal [CRC], 3; gastric, 2; small-cell lung [SCLC], 2; esophageal, prostatic, ovarian, non-small-cell lung, renal, tonsillar, urinary bladder, 1 each) after failing a median of 3 prior treatments (some including topoisomerase-I and -II inhibiting drugs). IMMU-132 was administered in repeated 21-day cycles, with each treatment given on days 1 and 8. Dosing started at 8 mg/kg/dose (i.e., 16 mg/kg/cycle), and escalated to 18 mg/kg before encountering dose-limiting neutropenia, in a 3+3 trial design. Fatigue, alopecia, and occasional mild to moderate diarrhea were some of the more common non-hematological toxicities, with 2 patients also reporting a rash. Over 80% of 24 assessable patients had stable disease or tumor shrinkage (17/24 SD; 3/24 PR) among the various metastatic cancers as best response by CT. Three patients (CRC, TNBC, SCLC) have PRs by RECIST; median TTP for all patients, excluding those with pancreatic cancer, is >18 weeks. Neutropenia has been controlled by dose reduction to 8-10 mg/kg/dose (16-20 mg/kg/cycle), which is the Phase II dose. Immunohistochemistry showed strong expression of Trop-2 in most archived patient tumors, but is not detected in serum. Corresponding reductions in blood tumor marker titers (e.g., CEA, CA19-9) reflected tumor responses. No anti-antibody or anti-SN-38 antibodies have been detected despite repeated dosing. Peak and trough assessments of IMMU-132 concentrations in the serum show that the conjugate clears completely within 7 days, an expected finding based on in vitro studies showing 50% of the SN-38 is released in the serum every day. These results indicate that this novel ADC, given in doses ranging from 16-24 mg/kg per cycle, is active in diverse metastatic solid cancers. A Phase II study is ongoing to determine response rates in CRC, TNBC, and SCLC, while also evaluating its potency in other tumor types.Citation Format: Alexander N. Starodub, Allyson J. Ocean, Manish A. Shah, Linda T. Vahdat, Ellen Chuang, Michael J. Guarino, Vincent J. Picozzi, Sajeve S. Thomas, Pius P. Maliakal, Serengulam V. Govindan, William A. Wegener, Robert M. Sharkey, David M. Goldenberg. SN-38 antibody-drug conjugate (ADC) targeting Trop-2, IMMU-132, as a novel platform for the therapy of diverse metastatic solid cancers: Initial clinical results. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT206. doi:10.1158/1538-7445.AM2014-CT206

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