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Gynecologic Oncology Aug 2004To evaluate immune responses and clinical outcomes for combined oregovomab and chemotherapy treatment of patients with recurrent ovarian cancer. (Clinical Trial)
Clinical Trial
OBJECTIVE
To evaluate immune responses and clinical outcomes for combined oregovomab and chemotherapy treatment of patients with recurrent ovarian cancer.
METHODS
Patients with advanced recurrent ovarian cancer were administered oregovomab over 12 weeks before chemotherapy, then optionally concurrent with chemotherapy x 2. Antibody responses, including human anti-mouse antibody (HAMA), anti-idiotypic antibody (Ab2) and anti-CA125, were assessed by ELISA; T-cell responses to CA125, autologous tumor and oregovomab by interferon (IFN)-gamma enzyme-linked immunoSPOT (ELISPOT) were also evaluated. Clinical outcomes were recorded.
RESULTS
Twenty patients were enrolled; median follow-up was 15.8 months. Oregovomab was well tolerated and did not produce drug-related serious adverse reactions. In 15/19 (79%) patients, robust treatment-emergent humoral responses were observed to the constant (HAMA) and variable region (Ab2) of oregovomab, and 2/19 (11%) patients developed anti-CA125 antibodies. Significant increases in T-cell responses were measured in 7/18 (39%) patients in response to CA125, in 5/8 (63%) patients in response to autologous tumor and in 9/18 (50%) patients in response to oregovomab. Immune responses appeared by week 12 (four doses) and were generally maintained or augmented in patients continuing combined treatment with oregovomab and chemotherapy. Median survival was 70.4 weeks (4.6-141.6 weeks), and the median progression-free interval was 11 weeks (2.6-114.6 weeks). Patients who mounted a T-cell response to CA125 and/or autologous tumor showed significantly improved survival (median not reached vs. 51.9 weeks, P = 0.002) compared to patients who did not.
CONCLUSIONS
Oregovomab was well tolerated and induced multiple antigen-specific immune responses, maintained during concomitant chemotherapy. A significant survival benefit was observed in patients mounting a T-cell response to CA125 and/or autologous tumor.
Topics: Aged; Antibodies, Monoclonal; CA-125 Antigen; Female; Humans; Immunization, Passive; Infusions, Intravenous; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; T-Lymphocytes
PubMed: 15297171
DOI: 10.1016/j.ygyno.2004.04.024 -
Cancer Immunology, Immunotherapy : CII Jul 2020The original version of this article unfortunately contained a mistake.
Correction to: Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients.
The original version of this article unfortunately contained a mistake.
PubMed: 32219502
DOI: 10.1007/s00262-020-02537-4 -
International Journal of Gynecological... 2005This prospective, open-label, pilot phase 2 study examined the clinical and immunologic effects of oregovomab (OvaRex) in heavily pretreated patients with recurrent...
This prospective, open-label, pilot phase 2 study examined the clinical and immunologic effects of oregovomab (OvaRex) in heavily pretreated patients with recurrent ovarian cancer (OC). Thirteen women were administered intravenous oregovomab (2 mg) at weeks 0, 2, 4, 8, and 12, followed by quarterly doses for up to 2 years or disease progression. Concomitant chemotherapy was not permitted. Eligibility criteria included recurrence after one or more platinum-based chemotherapy regimens, CA125 >35 U/mL, evaluable or measurable disease. Tumor burden was evaluated by physical or radiologic methods pretreatment, weeks 12, 24, and every 24 weeks thereafter. Immune responses, including antibodies and T cells to oregovomab and CA125, were demonstrated in over half the patients. Stabilization of disease and survival >2 years was observed in 3 of 13 patients and coincided with robust immune responses. Shrinkage of marker lesions was not observed; however, four patients showed decreases in CA125 levels. Treatment was well tolerated without serious adverse events or discontinuations due to therapy. This pilot study supports immunologic activity and safety of oregovomab in recurrent OC. Further study of this agent in the consolidation and adjuvant setting is ongoing to establish its clinical utility.
Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; CA-125 Antigen; Disease Progression; Female; Genital Neoplasms, Female; Humans; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Pilot Projects; Prospective Studies; Recurrence; Treatment Outcome
PubMed: 16343178
DOI: 10.1111/j.1525-1438.2005.00483.x -
Journal of Immunotherapy (Hagerstown,... 2008This report presents final survival survey results from a previously reported study using oregovomab immunotherapy in patients with advanced ovarian epithelial cancer.... (Randomized Controlled Trial)
Randomized Controlled Trial
CA125 velocity at relapse is a highly significant predictor of survival post relapse: results of a 5-year follow-up survey to a randomized placebo-controlled study of maintenance oregovomab immunotherapy in advanced ovarian cancer.
This report presents final survival survey results from a previously reported study using oregovomab immunotherapy in patients with advanced ovarian epithelial cancer. Follow-up surveys to 5 years from randomization were collected for the cohort of stage III/IV ovarian cancer patients achieving initial remission who received subsequent maintenance immunotherapy with oregovomab or placebo. The relationship of time-to-relapse, survival postrelapse, and overall survival was analyzed. One hundred forty-five patients in the intent-to-treat population and the hypothesis generating subset of 67 patients (debulked to < or =2 cm, CA125 < or =65 U/mL before cycle 3, normal CA125 and no evidence of disease postchemotherapy) previously reported were evaluated for long-term outcomes. Patterns of relapse and survival were consistent in both groups for the intent-to-treat population. Median survival time was 57.5 months for oregovomab and 48.6 months for placebo with an adjusted hazard ratio of 0.72 (95% confidence interval, 0.41-1.25). Median survival has not been reached in the hypothesis generating subset of patients receiving oregovomab. Cox multivariate regression analysis identified velocity of CA125 rise at relapse to be a highly statistically significant predictor of postrelapse outcome (P = 0.006). Although time-to-relapse may be a useful surrogate of survival in ovarian cancer immunotherapy studies, 5 years of follow-up has proved insufficient to permit a definitive survival analysis and it has been extended in ongoing phase III studies of oregovomab. Velocity of CA125 rise at relapse is a highly significant predictor of survival after relapse.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Cohort Studies; Female; Follow-Up Studies; Humans; Immunotherapy; Intracellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Proportional Hazards Models; Proteins; Recurrence; Survival Analysis
PubMed: 18481390
DOI: 10.1097/CJI.0b013e31816060ce -
Annals of Oncology : Official Journal... Feb 2014Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian cancer treatment. However, as mortality from advanced ovarian cancer remains very high,... (Review)
Review
Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian cancer treatment. However, as mortality from advanced ovarian cancer remains very high, novel therapies are required to be integrated into existing treatment regimens. Immunotherapy represents an alternative and rational therapeutic approach for ovarian cancer based on a body of evidence supporting a protective role of the immune system against these cancers, and on the clinical success of immunotherapy in other malignancies. Whether or not immunotherapy will have a role in the future management of ovarian cancer is too early to tell, but research in this field is active. This review will discuss recent clinical developments of selected immunotherapies for ovarian cancer which fulfil the following criteria: (i) they are antibody-based, (ii) target a distinct immunological pathway, and (iii) have reached the clinical trial stage. Specifically, the focus is on Catumaxomab (anti-EpCAMĂ—anti-CD3), Abagovomab, Oregovomab (anti-CA125), Daclizumab (anti-CD25), Ipilimumab (anti-CTLA-4), and MXD-1105 (anti-PD-L1). Catumaxomab has reached phase III clinical trials and exhibits promise with reports, showing that it can cause a significant and sustained reduction in ascites. Phase I-III clinical trials continue to be conducted on the other antibodies, some of which have had encouraging reports. We will also provide our perspective on the future of immunotherapy for ovarian cancer, and how it may be best employed in treatment regimens.
Topics: Animals; Antibodies, Bispecific; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Clinical Trials as Topic; Daclizumab; Diphtheria Toxin; Female; Humans; Immunoglobulin G; Immunotherapy; Interleukin-2; Ipilimumab; Ovarian Neoplasms; Recombinant Fusion Proteins
PubMed: 24285017
DOI: 10.1093/annonc/mdt405 -
Immunotherapy 2015Monoclonal antibodies remain a primary product option for novel cancer treatment. The properties of an antibody are a function of the antigen specificity and constant... (Review)
Review
Monoclonal antibodies remain a primary product option for novel cancer treatment. The properties of an antibody are a function of the antigen specificity and constant region incorporated. The rapid advance in molecular understanding of cancer biology and the host-tumor interaction has defined a new range of targets for antibody development. The clinical success of the checkpoint inhibitors has validated immune modulation and mobilization as a therapeutic approach. Solid cancers are distinguished from hematologic malignancies because the solid tumor stroma contains significant tumor promoting and immune dampening elements less prominent in hematologic cancer. This review highlights how engineered monoclonal antibody products are emerging as potential cornerstones of new more personalized cancer treatment paradigms that target both tumor and the stromal environment.
Topics: Antibodies, Monoclonal; Homeostasis; Humans; Immune System; Immunotherapy; Models, Immunological; Molecular Targeted Therapy; Neoplasms; Neovascularization, Pathologic
PubMed: 26314410
DOI: 10.2217/imt.15.57 -
Clinical & Developmental Immunology 2011During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies,... (Review)
Review
During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies, have emerged as an attractive option for the treatment of these malignancies. In fact, various molecular-targeted agents have been developed for a variety of malignancies with the objective to interfere with a precise tumor associated receptor, essential for cancer cell survival or proliferation, blocking its function, of the cancer cells. Alternatively, monoclonal antibodies have been developed to block immune suppression or enhance functions of immune effector cells. So far, several monoclonal antibodies have been tested for clinical efficacy for the treatment of gynecological cancers. Antibodies against Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) have been used in different neoplasms such as ovarian and cervical cancer. Catumazumab, a bivalent antibody against CD3 and EpCAM, is effective in the treatment of neoplastic ascites. Other antibodies are peculiar for specific cancer-associated antigen such as Oregovomab against CA125 or Farletuzumab against the folate receptor. Here we describe the preclinical and clinical experience gained up to now with monoclonal antibodies in tumors of the female genital tract and trace future therapeutic and research venues.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; ErbB Receptors; Female; Humans; Molecular Targeted Therapy; Ovarian Neoplasms; Receptors, Vascular Endothelial Growth Factor; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 22235224
DOI: 10.1155/2011/890758 -
Journal of Immunotherapy (Hagerstown,... Jan 2009Oregovomab is a monoclonal antibody that recognizes CA125 and forms circulating immune complexes that can elicit immunity against both tumor antigen and tumor. This... (Randomized Controlled Trial)
Randomized Controlled Trial
The Immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer.
Oregovomab is a monoclonal antibody that recognizes CA125 and forms circulating immune complexes that can elicit immunity against both tumor antigen and tumor. This study was designed to assess combining this immunotherapy at 2 dosing schedules with front-line chemotherapy in patients with advanced ovarian cancer. Forty patients with stage III/IV carcinomas were randomized to receive a 2 mg oregovomab infusion either the same day [simultaneous infusion (SIM)] or 1 week after [1-week delayed (OWD)] standard carboplatin-paclitaxel chemotherapy at cycles 1, 3, and 5, then quarterly for up to 11 antibody doses. The primary end point was antibody response to oregovomab. Secondary end points included cellular immune response, response rate to front-line treatment, and progression-free survival. A different immune response pattern was observed between the SIM arm and the OWD arm, baseline plasma cytokines were balanced. Humoral immunity occurred more rapidly (P=0.0033) and with greater magnitude in the SIM arm. Absolute lymphocyte counts decreased in the SIM arm at cycles 3 and 5 compared with baseline. Treatment emergent CA125-specific cellular immunity was measured more commonly with SIM (P=0.04) and clinical parameters directionally favored this schedule. The immune responses were stronger than those measured in a previous maintenance monoimmunotherapy protocol. Immunotherapy-associated toxicity was minimal in this study. Front-line chemotherapy with carboplatin-paclitaxel has immune adjuvant properties when combined with oregovomab immunotherapy; however, schedule is important. SIM strategies of carboplatin and paclitaxel should be further studied with oregovomab and other antigen-specific cancer immunotherapy approaches.
Topics: Adjuvants, Immunologic; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; Carboplatin; Cytokines; Dendritic Cells; Drug Administration Schedule; Female; Humans; Immunotherapy; Interferon-gamma; Kaplan-Meier Estimate; Middle Aged; Ovarian Neoplasms; Paclitaxel
PubMed: 19307994
DOI: 10.1097/CJI.0b013e31818b3dad -
Expert Review of Anticancer Therapy Feb 2005Despite advances in understanding and treatment, ovarian cancer remains a major cause of cancer mortality worldwide. Debulking surgery and paclitaxel/carboplatin... (Review)
Review
Despite advances in understanding and treatment, ovarian cancer remains a major cause of cancer mortality worldwide. Debulking surgery and paclitaxel/carboplatin chemotherapy induce good initial responses in most patients, although most cases of advanced disease are not controlled. Monoclonal antibodies hold promise as a potential incremental advance for the treatment of the disease. Antibodies can be used to stimulate the immune response, target tumor-specific receptors to induce antibody-dependent cellular cytotoxicity or interfere with biologic pathways. They can also be used to deliver therapeutic radioisotopes to malignant cells. Oregovomab is in Phase III clinical trials as a consolidation treatment post front-line therapy to trigger tumor-specific cellular immunity. Bevacizumab, which blocks vascular endothelial growth factor, will be entering Phase III as an adjuvant to front-line chemotherapy with a direct effect on angiogenesis. Additional immunostimulating, immune counter-regulatory and receptor-targeting approaches are also reviewed. The family of epidermal growth factor receptors including epidermal growth factor receptor 1 (HER-1) and 2 (HER-2) are both expressed in ovarian cancer and are the subject of ongoing research and development. The recent disappointing results with 90-yttrium-labeled anti-HMFG by single intraperitoneal administration have left the radiopharmaceutical field without a Phase III candidate. Identification of novel targets may advance this therapeutic area in the future. The rapid advances in the fields of immunoregulation and tumor biology should permit an accelerated introduction of antibodies for the treatment of ovarian cancer. These antibodies could complement novel small molecules that are also in development.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; ErbB Receptors; Female; Humans; Ovarian Neoplasms
PubMed: 15757441
DOI: 10.1586/14737140.5.1.87 -
Minerva Ginecologica Dec 2004Much of the current approaches in the treatment of advanced ovarian cancer are directed towards prolongation of duration between primary treatment and remission.... (Comparative Study)
Comparative Study Review
Much of the current approaches in the treatment of advanced ovarian cancer are directed towards prolongation of duration between primary treatment and remission. Immunotherapy is regarded as one attractive option for consolidation of initial therapeutic responses. In fact, immune reactivity against ovarian carcinoma can be induced by various immunotherapeutical approaches including antibodies, peptides or dendritic cell vaccines. This review provides an overview of recent clinical trials using various concepts of immunotherapy for the treatment of ovarian cancer. Possible reasons for limited clinical success as well as further progress to improve efficacy of current immune intervention strategies, e.g. by vaccines targeting a broader range of tumor-derived antigenic structures or activating diverse host immune functions, will be discussed.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antibody Specificity; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Cancer Vaccines; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cytokines; Dendritic Cells; Female; Follow-Up Studies; Humans; Immunologic Factors; Immunotherapy; Lymphocyte Activation; Ovarian Neoplasms; Peptides; Placebos; Prognosis; Radioimmunotherapy; Randomized Controlled Trials as Topic; T-Lymphocytes; Time Factors
PubMed: 15729204
DOI: No ID Found