Clinical Trials

Date: 2016-12-09

Type of information: Halting of the trial

phase: 2a

Announcement: halting of the trial

Company: BioInvent (Sweden)

Product: BI-505

Action mechanism:

• monoclonal antibody. BI-505 is a fully human antibody targeting ICAM-1, a protein on the surface of cancer cells. The substance’s good safety profile was documented in a phase I study in patients who were resistant to existing drugs and where there were also signs of a positive effect against the disease. Preclinical data shows improved activity against the tumour if the substance is administered in combination with the registered drugs Velcade® or Revlimid®.

Disease: multiple myeloma

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• The study is open-label, randomized, and includes a control group receiving only standard treatment. The open-label design will allow for patient outcomes to be monitored on an individual basis throughout the study. The primary efficacy evaluation of BI-505 will be made after 100 days with the primary endpoint being the proportion of patients in stringent complete response (sCR). Patients will thereafter be followed over three years to document progression-free survival (PFS). As a secondary endpoint, patients will also be monitored for any residual, disease known as "Minimal Residual Disease" (MRD), to assess deep responses. (NCT02756728 )

Latest news:

• • On December 9, 2016, BioInvent International announces that it has decided to terminate its current clinical Phase II study with BI-505 in multiple myeloma. The decision follows BioInvent’s review and discussion with the FDA, who put BI-505 on full clinical hold in November 2016.
• The terminated trial, which was performed in collaboration with Penn Medicine, targeted a specific population of multiple myeloma patients undergoing autologous stem cell transplantation with high-dose melphalan.
• • On November 8, 2016, BioInvent International has received verbal notice from the FDA that a full clinical hold (i.e. no further dosing of patients) has been placed on BioInvent’s current clinical Phase II study with the antibody BI-505 in patients with multiple myeloma. BioInvent has not yet received written notice of the clinical hold from the FDA, however, based on verbal communications, the FDA informed BioInvent that the clinical hold is due to an adverse cardiopulmonary event in the clinical study. The clinical study is being conducted by BioInvent in collaboration with investigators at the University of Pennsylvania in the United States and aims to document the ability of BI-505 to deepen therapeutic response and thereby prevent or delay relapse of multiple myeloma in patients undergoing autologous stem cell transplantation (ASCT) with high-dose melphalan.
• BioInvent will analyse the possibility to obtain release of the clinical hold and markets will be updated when there is further information to report.
• • On April 18, 2016, BioInvent International announced that patient recruitment into the trial can now start in the upcoming clinical Phase II study with the antibody BI-505 in patients with multiple myeloma, as necessary regulatory approvals have been obtained. The first patient is expected to be dosed in May. The clinical study will be conducted by BioInvent in collaboration with investigators at the University of Pennsylvania in the United States. It aims to document the ability of BI-505 to deepen the therapeutic response and thereby prevent or delay relapse of multiple myeloma in patients undergoing autologous stem cell transplantation (ASCT) with high-dose melphalan as part of their standard of care. The study will enroll approximately 90 patients undergoing ASCT whereof half will receive BI-505 as an add-on treatment to their standard of care.
• •  On September 21, 2015, BioInvent International  announced that the company and its partner, the University of Pennsylvania, have decided to expand their planned clinical Phase II study with the antibody BI-505 by, among other things, including a control group. This will increase the study data quality and accelerate the path for approval of a potential new drug for multiple myeloma. As a result of more effective treatments being available, the multiple myeloma survival rate has increased significantly over the past 20 years. However, neither existing nor new drugs in clinical development are expected to be able to eliminate all myeloma cells, and residual cells lead to relapse in the vast majority of patients with the disease. Data from preclinical studies indicate that the mechanism-of-action of BioInvent’s antibody BI-505, to engage the immune system to seek up and attack stressed cancer cells, has the potential to significantly improve responses and prevent or delay relapse. The positive safety profile of BI-505, which has been documented in an earlier clinical trial, is an important factor in making BI-505 well-suited for patients who are undergoing autologous stem cell transplant (ASCT). The Phase II controlled study will include patients undergoing ASCT and chemotherapy with high-dose melphalan (HDM). The number of patients receiving supplementary treatment with BI-505 will be increased to 45 patients, up from the previously announced 30. In addition, a control group of a total of 45 patients will be added to the study. These patients will receive the standard of care treatment. Altogether the number of patients in the study is being tripled compared to the previously communicated plan. The greater patient numbers will allow for a more accurate evaluation of the effect of supplementary therapy with BioInvent’s antibody. The study will begin with a safety evaluation of five patients, which is in keeping with the original plan, and will also include an interim analysis. The clinical effect of BI-505 will be evaluated 100 days after transplantation and after one year. All patients will also be monitored for up to five years to evaluate progression-free survival.
• •  On March 19, 2015, BioInvent International completed a strategic analysis of its ICAM-1 targeted phase II antibody BI-505 with thought leaders to garner support on the development of BI-505. Based on the analysis of BI-505’s data, a clear direction emerged that BI-505 is uniquely positioned to increase the potential depth and quality of response in patients receiving standard of care treatment for multiple myeloma. Many multiple myeloma patients initially achieve a good response from existing therapy; however, patients can eventually relapse and succumb to the cancer as a consequence of myeloma cells that remain in the patient after treatment (minimal residual disease). BioInvent intends to conduct a Phase IIa study in multiple myeloma patients that have undergone autologous stem cell transplantation (ASCT) to investigate the ability of BI-505 to increase the depth and quality of response after ASCT in combination with standard of care. Results from the open-label trial will be compared to a historical data from a matched cohort of patients. The intention is to recruit approximately 30 patients, and study start is planned for early 2016. The study will be conducted as an investigator sponsored study in close collaboration with leading clinicians at the Abramson Cancer Center of the, University of Pennsylvania. As a consequence of this strategic analysis of the potential of BI-505 in multiple myeloma patients post ASCT, BioInvent will conclude the its smouldering myeloma study. Smouldering myeloma does not constitute a relevant commercial development opportunity for BioInvent, and the mechanism of action of BI-505 is not believed to be as relevant in this indication.

Is general: Yes