Date: 2014-11-10
Type of information: Initiation of the trial
phase: 1b
Announcement: initiation of the trial
Company: Oncothyreon (USA - WA) Celldex Therapeutics (USA - NJ)
Product: ONT-10 and Varlilumab
Action
mechanism: ONT-10 is a therapeutic vaccine targeting MUC1, a tumor-associated antigen present on many types of human malignant tumors, including lung, breast, colorectal, prostate and ovarian cancer. ONT-10 contains a glycosylated antigen designed to mimic the hypoglycosylated state of tumor-associated MUC1 and intended to stimulate both the humoral and cellular arms of the immune response. Additionally, ONT-10 contains the adjuvant PET-Lipid A, a fully synthetic toll like receptor 4 (TLR4) agonist proprietary to Oncothyreon. In an ongoing Phase 1 trial ONT-10 has been well-tolerated, has led to a robust anti-MUC1 antibody response, and has been associated with prolonged stable disease of greater than six months in advanced stage patients. Oncothyreon is continuing the Phase 1 trial and is currently enrolling two disease-specific cohorts in patients with advanced breast or ovarian carcinoma. Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. CD27 can be effectively manipulated with activating antibodies to induce potent anti-tumor responses, and may result in less toxicities due to its restricted expression and regulation. In preclinical studies, stimulation of CD27 in combination with vaccines increased the quality and magnitude of the T-cell response. Varlilumab is a potent anti-CD27 agonist that induces activation and proliferation of human T cells when combined with T-cell receptor stimulation. In lymphoid malignancies that express CD27 at high levels, varlilumab has an additional mechanism through a direct anti-tumor effect. In ongoing Phase 1 trials varlilumab has shown an excellent safety profile and demonstrated clear biologic activity and promising signs of clinical activity in an advanced, refractory patient population.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The trial is an open-label Phase 1b study of ONT-10 administered at the recommended single agent dose in combination with varlilumab at two dose levels in up to 42 patients with advanced breast or ovarian cancer. The primary objective of the trial is to determine the safety and tolerability of the combined therapy. Additional objectives include evaluations of the impact of combination treatment on MUC1-specific humoral and cellular immune responses, T-cell activation markers and levels of regulatory T-cells, and anti-tumor effects. (NCT0227037)
Latest
news: * On November 10, 2014, Oncothyreon and Celldex Therapeutics announced that they have initiated a combined clinical trial of ONT-10 and varlilumab. ONT-10 is a therapeutic vaccine targeting the tumor-associated antigen MUC1. Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. The Phase 1b trial will be conducted by Oncothyreon under the terms of a previously announced collaboration agreement between Oncothyreon and Celldex. The two companies will jointly own the data from the trial and will make any plans for potential future development of the combination therapy together. Under the agreement, neither company has granted the other a license, or any other rights, to its product candidate.
