January 29, 2015 I Celldex Therapeutics, Inc. (NASDAQ: CLDX) and Bristol Myers-Squibb (NYSE: BMY) today announced the initiation of a Phase 1/2 dose escalation and cohort expansion study examining the investigational combination of varlilumab, Celldex’s CD27 targeting investigational immune-activating antibody and Bristol-Myers Squibb’s immunotherapy Opdivo (nivolumab). The study will be conducted in adult patients with advanced non-small cell lung cancer (NSCLC), metastatic melanoma (MEL), colorectal cancer (CRC), ovarian cancer, and head and neck squamous cell carcinoma (SCCHN). Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. This study will evaluate the safety and tolerability of the combination and address the hypothesis that the combination of these two mechanisms enhance the anti-tumor activity compared to either agent alone. Celldex is responsible for conducting the study and development costs will be shared.
The Phase 1 dose-escalation portion of the study will assess the safety and tolerability of varlilumab at doses ranging from 0.1 to 10 mg/kg when administered with Opdivo (3mg/kg). Following dose escalation, a Phase 2 portion of the study will include 5 disease specific cohorts, with either 18 (CRC, SCCHN, ovarian) or 35 (NSCLC and MEL) patients in each cohort. Patients will be treated with varlilumab until intolerance, disease progression or completion of up to 4 cycles. There is no limit on the duration of treatment with Opdivo. The primary objective of the Phase 2 study is overall response rate. Secondary objectives include pharmacokinetics assessments, determining the immunogenicity of varlilumab when given in combination with Opdivo and further assessing the anti-tumor activity of combination treatment, including duration of response, time to response, progression-free survival and overall survival.
About Varlilumab
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 fewer toxicities due to its restricted expression and regulation. 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 may have an additional mechanism of action through a direct anti-tumor effect. Varlilumab has completed a Phase 1 dose-escalation study, demonstrating potent immunologic activity consistent with its mechanism of action and anti-tumor activity in patients with advanced, refractory disease. No maximum tolerated dose was reached and minimal toxicities were observed. Celldex has initiated a broad development program for varlilumab to explore its role as an immune activator in combination with a number of complementary investigational and approved oncology drugs. Varlilumab is currently being studied in two Phase 1/2 combination studies and several additional combination studies will be initiated in 2015.
About OPDIVO (Nivolumab)
The U.S. Food and Drug Administration (FDA) approved Opdivo (nivolumab) injection, for intravenous use. Opdivo is a PD-1 blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide.
About Celldex Therapeutics, Inc.
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline is built from a proprietary portfolio of antibodies and immunomodulators used alone and in strategic combinations to create novel, disease-specific therapies that induce, enhance or suppress the body’s immune response. Visit http://www.celldex.com/.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
SOURCE: Bristol-Myers Squibb
Post Views: 49
January 29, 2015 I Celldex Therapeutics, Inc. (NASDAQ: CLDX) and Bristol Myers-Squibb (NYSE: BMY) today announced the initiation of a Phase 1/2 dose escalation and cohort expansion study examining the investigational combination of varlilumab, Celldex’s CD27 targeting investigational immune-activating antibody and Bristol-Myers Squibb’s immunotherapy Opdivo (nivolumab). The study will be conducted in adult patients with advanced non-small cell lung cancer (NSCLC), metastatic melanoma (MEL), colorectal cancer (CRC), ovarian cancer, and head and neck squamous cell carcinoma (SCCHN). Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. This study will evaluate the safety and tolerability of the combination and address the hypothesis that the combination of these two mechanisms enhance the anti-tumor activity compared to either agent alone. Celldex is responsible for conducting the study and development costs will be shared.
The Phase 1 dose-escalation portion of the study will assess the safety and tolerability of varlilumab at doses ranging from 0.1 to 10 mg/kg when administered with Opdivo (3mg/kg). Following dose escalation, a Phase 2 portion of the study will include 5 disease specific cohorts, with either 18 (CRC, SCCHN, ovarian) or 35 (NSCLC and MEL) patients in each cohort. Patients will be treated with varlilumab until intolerance, disease progression or completion of up to 4 cycles. There is no limit on the duration of treatment with Opdivo. The primary objective of the Phase 2 study is overall response rate. Secondary objectives include pharmacokinetics assessments, determining the immunogenicity of varlilumab when given in combination with Opdivo and further assessing the anti-tumor activity of combination treatment, including duration of response, time to response, progression-free survival and overall survival.
About Varlilumab
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 fewer toxicities due to its restricted expression and regulation. 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 may have an additional mechanism of action through a direct anti-tumor effect. Varlilumab has completed a Phase 1 dose-escalation study, demonstrating potent immunologic activity consistent with its mechanism of action and anti-tumor activity in patients with advanced, refractory disease. No maximum tolerated dose was reached and minimal toxicities were observed. Celldex has initiated a broad development program for varlilumab to explore its role as an immune activator in combination with a number of complementary investigational and approved oncology drugs. Varlilumab is currently being studied in two Phase 1/2 combination studies and several additional combination studies will be initiated in 2015.
About OPDIVO (Nivolumab)
The U.S. Food and Drug Administration (FDA) approved Opdivo (nivolumab) injection, for intravenous use. Opdivo is a PD-1 blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide.
About Celldex Therapeutics, Inc.
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline is built from a proprietary portfolio of antibodies and immunomodulators used alone and in strategic combinations to create novel, disease-specific therapies that induce, enhance or suppress the body’s immune response. Visit http://www.celldex.com/.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
SOURCE: Bristol-Myers Squibb
Post Views: 49
