SBIR-STTR Award

The main goal of this Phase I/II SBIR application is to translate rapidly preclinical findings that show the advantage of using a combination radioimmunotherapy plus immunotherapy treatment regimen that uses non-competing antibodies for the improved treatment of aggressive non-Hodgkin's lymphoma [NHL; i.e., diffuse large B-cell lymphoma (DLBCL) and mantle cell (MC)] patients prior to or in place of a high-dose chemotherapy/transplant. This treatment paradigm is intended to provide a meaningful treatment alternative for aggressive NHL Phase I/II clinical trials with 90Y-epratuzumab (humanized anti-CD22 IgG) and veltuzumab (humanized anti-CD20 IgG) have established the maximum tolerated dose (MTD) of a fractionated injection of 90Y-epratuzumab, and the optimal biological dose of veltuzumab, with both agents showing encouraging anti-tumor responses in follicular and aggressive NHL. This study first will re-evaluate the MTD for the fractionated weekly injection of 90Y-epratuzumab (previously found to be 2 x 20 mCi/m2) in a standard Phase I setting, and then proceed immediately into a Phase II trial to evaluate response and safety. The treatment regimen consists of 2 courses of veltuzumab spaced 4 weeks apart, with each course consisting of 4 weekly 120 mg/m2 of veltuzumab). 90Y-epratuzumab will be co-injected with the 3rd and 4th veltuzumab injection during the first veltuzumab course. This treatment regimen is based on preclinical data showing how a consolidation treatment with veltuzumab amplifies the treatment response of a radioconjugate treatment, but also how current anti-CD20-based radioimmunotherapy regimens may be reducing the impact of the therapeutic response by co-administered large amounts of competing anti-CD20 IgG. By substituting a 90Y-anti-CD22 radioconjugate, we can gain greater benefit from the radioconjugate and still provide the immunotherapeutic boost in response. Thus, this treatment scheme optimizes the use of both the radio- and immuno-conjugate for treating NHL. Standard pharmacokinetics and imaging studies will be performed in addition to safety and efficacy monitoring. 111In-epratuzumab imaging studies will be performed before the first veltuzumab treatment and with the first 90Y-epratuzumab injection to determine if there are any changes in biodistribution as a result of the prior veltuzumab injections. With encouraging results from this study, the company expects to initiate a registration trial.

Public Health Relevance:
This project will assess the safety and efficacy of a new combination radioimmunotherapy and immunotherapy treatment paradigm that will be applied to aggressive non-Hodgkin lymphoma. The treatment consists of a fractionated 90Y-DOTA-humanized anti-CD22 IgG (epratuzumab) given in combination with a humanized anti-CD20 IgG (veltuzumab), given in conjunction with the radioimmunotherapy, as well as a consolidation follow-up.

Public Health Relevance Statement:
This project will assess the safety and efficacy of a new combination radioimmunotherapy and immunotherapy treatment paradigm that will be applied to aggressive non-Hodgkin lymphoma. The treatment consists of a fractionated 90Y-DOTA-humanized anti-CD22 IgG (epratuzumab) given in combination with a humanized anti-CD20 IgG (veltuzumab), given in conjunction with the radioimmunotherapy, as well as a consolidation follow-up.

Project Terms:
ATGN; Active Follow-up; Aged 65 and Over; Antibodies; Antibody Formation; Antibody Production; Antibody Response; Antibody Therapy; Antigens; Arm; B blood cells; B lymphoma; B-Cell Lymphomas; B-Cell Non-Hodgkin's Lymphoma; B-Cell NonHodgkins Lymphoma; B-Cells; B-Lymphocytes; Biodistribution; Biological; Bp35; Bursa-Dependent Lymphocytes; Bursa-Equivalent Lymphocyte; C2B8 Monoclonal Antibody; CD20; Cancer Center; Cancer, Oncology; Cancers; Cell Count; Cell Number; Cells; Chemical Fractionation; Clinical; Clinical Investigator; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Phase II; Clinical Trials, Unspecified; Combined Modality Therapy; Controlled Study; Cytofluorometry, Flow; DLBCL; Data; Diffuse Large B-Cell Lymphoma; Diffuse non-Hodgkin's lymphoma, large cell; Disease; Disease Resistance; Disorder; Doctor of Philosophy; Dose; Drug Kinetics; Elderly; Elderly, over 65; Ensure; Epratuzumab; Epratuzumab (hLL2); FRACN; Flow Cytofluorometries; Flow Cytometry; Flow Microfluorimetry; Fractionation; Fractionation Radiotherapy; Gamma Camera Imaging; Gamma Globulin, 7S; Germinoblastoma; Goals; High Dose Chemotherapy; Humanized Anti-CD22 Monoclonal Antibody IgG1; ITX; Ibritumomab Tiuxetan; IgG; Image; Immunoglobulin G; Immunologically Directed Therapy; Immunoradiotherapy; Immunotherapeutic agent; Immunotherapy; Immunotherapy, Cancer, Radioisotope; Infusion; Infusion procedures; Injection of therapeutic agent; Injections; Investigators; Journals; Label; Leu-16; LymphoCide; Lymphoma; Lymphoma (Hodgkin's and Non-Hodgkin's); Lymphoma, Malignant; Lymphoma, Non-Hodgkin's; Lymphoma, Nonhodgkins; MS4A1; MS4A1 gene; MS4A2; Magazine; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Maximal Tolerated Dose; Maximally Tolerated Dose; Maximum Tolerated Dose; Medical; Mice; Microfluorometry, Flow; Moab, Clinical Treatment; Monitor; Monoclonal Antibodies; Multimodal Therapy; Multimodal Treatment; Multimodality Treatment; Murine; Mus; Myron; Myron (drug combination); New Agents; Non-Hodgkin's Lymphoma; Patients; Peripheral; Ph.D.; PhD; Pharmacokinetics; Phase; Phase 2 Clinical Trials; Phase II Clinical Trials; Position; Positioning Attribute; Principal Investigator; Progenitor Cell Transplantation; Protocols, Treatment; Publications; RGM; Radiation; Radio; Radio Conjugates; Radioconjugate; Radioimmunotherapy; Radionuclide Imaging; Refractory; Regimen; Relapse; Research Personnel; Researchers; Residual Tumors; Resistance; Resistance, Disease; Resort; Reticulolymphosarcoma; Retreatment; Rituximab (C2B8 Antibody); Roswell Park Cancer Institute; SBIR; SBIRS (R43/44); Safety; Salvage Therapy; Salvage-Tx; Sarcoma, Germinoblastic; Scanning, Radioisotope; Scheme; Scientific Publication; Scintigraphy; Secondary to; Small Business Innovation Research; Small Business Innovation Research Grant; Stem Cell Transplantation; Stem cell transplant; Therapeutic; Translating; Translatings; Transplantation; Treatment Protocols; Treatment Regimen; Treatment Schedule; Tumors, Residual; Upper arm; advanced age; alternative treatment; antibody biosynthesis; base; chemotherapy; clinical investigation; combination therapy; combined modality treatment; combined treatment; design; designing; disease/disorder; elders; experience; flow cytophotometry; follow-up; geriatric; hLL2; hLL2 agent; imaging; immune therapy; immunogen; immunoglobulin biosynthesis; immunologic preparation; immunotherapeutics; improved; language translation; large cell Diffuse non-Hodgkin's lymphoma; late life; later life; malignancy; meetings; multimodality therapy; neoplasm/cancer; non-Hodgkin's lymphoma; non-Hodgkins disease; non-Hodgkins lymphoma; novel; older adult; older person; oncology; phase 2 study; phase 2 trial; phase II trial; pre-clinical; preclinical; preclinical study; protocol, phase II; public health relevance; radionuclide imaging/scanning; radionuclide scanning; ray (radiation); residual disease; resistance to disease; resistant; resistant disease; resistant to disease; response; rituximab; senior citizen; standard care; study, phase II; transplant; treatment response; tumor; uptake

The main goal of this Phase I/II SBIR application is to translate rapidly preclinical findings that show the advantage of using a combination radioimmunotherapy plus immunotherapy treatment regimen that uses non-competing antibodies for the improved treatment of aggressive non-Hodgkin's lymphoma [NHL; i.e., diffuse large B-cell lymphoma (DLBCL) and mantle cell (MC)] patients prior to or in place of a high-dose chemotherapy/transplant. This treatment paradigm is intended to provide a meaningful treatment alternative for aggressive NHL Phase I/II clinical trials with 90Y-epratuzumab (humanized anti-CD22 IgG) and veltuzumab (humanized anti-CD20 IgG) have established the maximum tolerated dose (MTD) of a fractionated injection of 90Y-epratuzumab, and the optimal biological dose of veltuzumab, with both agents showing encouraging anti-tumor responses in follicular and aggressive NHL. This study first will re-evaluate the MTD for the fractionated weekly injection of 90Y-epratuzumab (previously found to be 2 x 20 mCi/m2) in a standard Phase I setting, and then proceed immediately into a Phase II trial to evaluate response and safety. The treatment regimen consists of 2 courses of veltuzumab spaced 4 weeks apart, with each course consisting of 4 weekly 120 mg/m2 of veltuzumab). 90Y-epratuzumab will be co-injected with the 3rd and 4th veltuzumab injection during the first veltuzumab course. This treatment regimen is based on preclinical data showing how a consolidation treatment with veltuzumab amplifies the treatment response of a radioconjugate treatment, but also how current anti-CD20-based radioimmunotherapy regimens may be reducing the impact of the therapeutic response by co-administered large amounts of competing anti-CD20 IgG. By substituting a 90Y-anti-CD22 radioconjugate, we can gain greater benefit from the radioconjugate and still provide the immunotherapeutic boost in response. Thus, this treatment scheme optimizes the use of both the radio- and immuno-conjugate for treating NHL. Standard pharmacokinetics and imaging studies will be performed in addition to safety and efficacy monitoring. 111In-epratuzumab imaging studies will be performed before the first veltuzumab treatment and with the first 90Y-epratuzumab injection to determine if there are any changes in biodistribution as a result of the prior veltuzumab injections. With encouraging results from this study, the company expects to initiate a registration trial.

Public Health Relevance:
This project will assess the safety and efficacy of a new combination radioimmunotherapy and immunotherapy treatment paradigm that will be applied to aggressive non-Hodgkin lymphoma. The treatment consists of a fractionated 90Y-DOTA-humanized anti-CD22 IgG (epratuzumab) given in combination with a humanized anti-CD20 IgG (veltuzumab), given in conjunction with the radioimmunotherapy, as well as a consolidation follow-up.

Public Health Relevance Statement:
This project will assess the safety and efficacy of a new combination radioimmunotherapy and immunotherapy treatment paradigm that will be applied to aggressive non-Hodgkin lymphoma. The treatment consists of a fractionated 90Y-DOTA-humanized anti-CD22 IgG (epratuzumab) given in combination with a humanized anti-CD20 IgG (veltuzumab), given in conjunction with the radioimmunotherapy, as well as a consolidation follow-up.

Project Terms:
alternative treatment; Antibodies; Antibody Formation; Antibody Therapy; Antigens; arm; B-Cell Lymphomas; B-Lymphocytes; base; Biodistribution; Biological; Cancer Center; CD22 gene; Cell Count; Cells; chemotherapy; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Combined Modality Therapy; Controlled Study; Data; design; Disease; Disease Resistance; Doctor of Philosophy; Dose; Drug Kinetics; Elderly; Ensure; Epratuzumab; experience; Flow Cytometry; follow-up; Fractionation; Goals; Health; High Dose Chemotherapy; Ibritumomab Tiuxetan; Image; Immunoglobulin G; Immunotherapeutic agent; Immunotherapy; improved; Infusion procedures; Injection of therapeutic agent; Journals; Label; large cell Diffuse non-Hodgkin's lymphoma; Lymphoma; Malignant Neoplasms; Maximum Tolerated Dose; Medical; meetings; Monitor; Monoclonal Antibodies; MS4A1 gene; Mus; Myron (drug combination); New Agents; Non-Hodgkin's Lymphoma; novel; oncology; Patients; Peripheral; Phase; Phase II Clinical Trials; Positioning Attribute; pre-clinical; preclinical study; Principal Investigator; Publications; Radiation; Radiation therapy; Radioconjugate; Radioimmunotherapy; Radionuclide Imaging; Refractory; Regimen; Relapse; Research Personnel; Residual Tumors; Resistance; Resort; response; Retreatment; rituximab; Roswell Park Cancer Institute; Safety; Salvage Therapy; Scheme; Secondary to; Small Business Innovation Research Grant; standard care; Stem cell transplant; Therapeutic; Translating; Transplantation; treatment duration; Treatment Protocols; treatment response; tumor; uptake