Date: 2014-09-18
Type of information: Completion of patient enrollment
phase: 1b
Announcement: completion of patient enrollment
Company: Argen-X (The Netherlands-Belgium)
Product: ARGX-110
Action mechanism: monoclonal antibody/immune checkpoint inhibitor. ARGX-110 is a first-in-class CD70-targeting monoclonal antibody that addresses both known mechanisms of action mediated by CD70: tumor cell proliferation and survival and tumor cell escape from immune surveillance. In addition, POTELLIGENT® enhanced Antibody Dependent Cellular Cytotoxicity (ADCC) of ARGX-110 drives the selective destruction of CD70 positive tumor cells. In preclinical testing, ARGX-110 has shown broad therapeutic potential against CD70 positive lymphomas and lymphocytic leukemias, as well as solid tumors including those caused by oncogenic viruses, such as nasopharyngeal, cervical, and hepatocellular carcinomas.
Disease: CD70-positive hematological and virally-induced solid tumors
Therapeutic area: Cancer - Oncology
Country: Belgium, France
Trial details: The Phase Ib study consists of a dose escalation followed by adaptive safety and efficacy expansion cohorts conducted in patients with advanced, refractory cancer. The patient enrichment strategy relies on individual tumor screening for CD70 utilizing a reproducible immunohistochemistry method. In addition to traditional clinical and PK/PD endpoints, biomarkers documenting the three modes of action of ARGX-110 are being evaluated. Patient enrolment is planned at 90 CD70-positive patients with either haematological or solid tumors. The open-label Phase Ib expansion aims to enrol up to 75 patients at three clinical centers in Belgium (Institut Jules Bordet, UZA, and UZG) and Institut Gustave Roussy in France. (NCT01813539)
Latest news: * On September 18, 2014, Argen-X announced that the company has completed enrolment of a first cohort of 15 patients with CD70-positive solid tumors into an open-label Phase 1b expansion trial with ARGX-110. Recruitment of a second cohort of 15 patients with CD70-positive hematological malignancies is ongoing. The primary objective of the expansion trial is to select one or more indications to take forward into further clinical trials. The company expects to report topline results from the expansion phase of the trial and select indications for further clinical studies in the second half of 2015. In the initial dose-escalation phase of the Phase 1b study, ARGX-110 demonstrated a good safety profile with no dose-limiting toxicities seen in the 26 patients treated. Encouraging signs of efficacy were also observed, and as of September 2014, prolonged stabilization of disease (progression-free survival of six months or longer) was observed in five patients with renal cell carcinoma, platinum-refractory ovarian cancer, head and neck cancer, myoepithelial carcinoma and mesothelioma, respectively. Two of these patients demonstrated stable disease for over 12 months. In addition, activity was seen in two patients with distinct forms of T-cell lymphoma, one a complete response (CR) in a patient with Sézary syndrome. * On May 29, 2014, arGEN-X will present full results from the dose-escalation part of a Phase 1 study of ARGX-110, a novel anti-CD70 antibody, in patients with advanced hematological and solid tumors at the 50th annual meeting of the American Society of Clinical Oncology (ASCO; 30 May-3 June, 2014, Chicago, IL, USA). The company reported in December 2013 that this study met its translational development goals: all pre-specified biological activity measures (e.g. target saturation, effector functions, immune-modulation) were met. The study also showed that ARGX-110 has a favorable safety profile and identified a dose that was advanced into a larger safety study in patients with a range of hematological and solid tumors. Patient recruitment into this expanded study began in January 2014 in Europe and top-line results are expected in 2015. The results will be presented in a poster as follows: Abstract number: #3023 - Poster title: A Phase 1, first-in-human study of ARGX-110, a monoclonal antibody targeting CD70, a receptor involved in immune escape and tumor growth in patients with solid and hematological malignancies.Presenter: Ahmad Awada, Principal Investigator, Institut Jules Bordet * On January 13, 2014, arGEN-X, a clinical stage human therapeutic antibody company, has announced that it has advanced ARGX-110, a novel anti-CD70 antibody, into the safety and efficacy expansion part of its Phase Ib study. The objective is to further investigate the safety of ARGX-110 in CD70-positive cancer patients with either haematological or solid tumors, and to evaluate efficacy in order to select the indications to be studied in Phase II clinical development. Top-line results are expected in about 12 months. The study is being supported by a €3.5 million grant from the Flemish Government’s Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT). In the first part of the Phase Ib study, announced in December 2013, ARGX-110 showed a favorable safety profile, exhibited no dose-limiting toxicities and met all translational development goals (i.e. measures of biological activity such as target engagement, effector functions, and immune-modulation). The expansion phase is part of a broader ‘Transformational Medical Research’ (TGO) project implemented by arGEN-X in close collaboration with leading Flemish research organizations and clinical centers and supported by IWT. The project aims to develop and further the use of innovative, adaptive clinical trial designs that leverage immunohistochemistry, biomarkers, tissue bank materials as well as clinical data to improve the chances of success with novel drug candidates. The project also involves leading academic research on CD70/CD27 signaling for expanding the field of cancer immunotherapy. * On December 17, 2013, arGEN-X has announced that the dose-escalation part of a Phase Ib study with its lead antibody ARGX-110 has met its translational development goals: all pre-specified biological activity measures (e.g. target engagement, effector functions, immune-modulation) were met. The study also showed that ARGX-110 has a favourable safety profile and a dose has been selected to advance into the Phase Ib safety and efficacy expansion cohorts, which will start early in 2014 and are expected to report top-line results approximately 12 months later. In the study, 19 patients with CD70-positive cancer were treated with escalating doses of ARGX-110, up to 10 mg/kg. The results show predictable pharmacokinetics across the dose range. No dose-limiting toxicity was identified. Based on these data, arGEN-X will begin enrolment to hematology and solid tumor safety and efficacy expansion cohorts early in 2014 and report top-line results approximately 12 months later. According to Alain Thibault, MD, Chief Medical Officer, “We have consistent biomarker data that confirms our understanding of CD70 and the three mechanisms of action of ARGX-110. This is speeding up our program, and we may be in a position to select promising indications for Phase II development by the end of 2014.” * On January 7 2013, arGEN-X, a biopharmaceutical company specialized in the discovery and development of highly differentiated human monoclonal antibody therapeutics, has announced the initiation of a Phase Ib first-in-man cancer study with ARGX-110, its first SIMPLE Antibody™ program to enter the clinic in just three years from initiation of discovery. The Phase Ib study will utilize a validated immunohistochemistry test to pre-screen patients for those whose tumors show up-regulation of CD70. In addition to traditional clinical and PK endpoints, biomarkers critical to understanding CD70 biology will be researched extensively in the course of the trial. Results on the recommended dose for future pivotal trials are expected by end Q4, 2013. In preclinical testing, ARGX-110 has shown broad therapeutic potential against CD70 positive lymphomas and lymphocytic leukemias, as well as solid tumors including those caused by oncogenic viruses, such as nasopharyngeal, cervical, and hepatocellular carcinomas. In November 2012, arGEN-X filed a first CTA for ARGX-110, in hematological and virally-induced solid tumors, as well as in autoimmunity.
