NEW YORK—Seattle Genetics Inc. and Bristol-Myers Squibb have begun a Phase 1/2 clinical trial of ADCETRIS (brentuximab vedotin) in combination with Opdivo (nivolumab) for patients with CD30-expressing relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). This is the second of two trials being conducted under a previously announced clinical trial collaboration agreement between the companies.
“Bristol-Myers Squibb continues to strengthen its industry-leading development program for Opdivo and its rapidly expanding hematology portfolio,” Michael Giordano, senior vice president, head of Development, Oncology for Bristol-Myers Squibb, said in a press release. “We are pleased to collaborate with Seattle Genetics on clinical research that focuses on novel combination regimens in areas of serious unmet need.”
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a marker expressed on Hodgkin lymphoma (HL) and several types of NHL, which combines the targeting ability of a monoclonal antibody with a highly potent cell-killing agent. Recent preclinical data suggest that ADCETRIS causes immunogenic cell death of tumor cells, providing rationale for combination with the checkpoint inhibitor Opdivo, a human antibody that targets and inhibits the programmed death receptor-1, resulting in T-cell activation.
“This is the second corporate-sponsored clinical trial to evaluate ADCETRIS combined with a checkpoint inhibitor to determine if the combination can improve patient outcomes,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “This study is a part of a broad development program that includes more than 70 ongoing clinical trials evaluating ADCETRIS in multiple lines of therapy for Hodgkin and non-Hodgkin lymphoma and as part of novel combinations that could result in improved clinical benefit with manageable safety profiles. Our goal is to establish ADCETRIS as the foundation of care for CD30-expressing lymphomas.”
The Phase 1/2 open-label, multi-center, clinical trial is designed to evaluate the safety, tolerability and antitumor activity of ADCETRIS in combination with Opdivo in patients with relapsed or refractory CD30-expressing NHL. The study will consist of a Phase 1 dose evaluation portion followed by a single-arm Phase 2 portion that will expand enrollment to treat disease-specific cohorts with relapsed or refractory DLBCL, PTCL or CTCL at the recommended dose level and treatment schedule. The primary endpoints are safety, tolerability and objective response rate of the combination of ADCETRIS with Opdivo. The secondary endpoints include duration of response, complete response rate with the combination regimen, duration of complete response, progression-free survival and overall survival. The trial is being conducted at multiple centers in the United States, Canada and Europe and is designed to enroll approximately 120 patients.
ADCETRIS is currently being evaluated in more than 70 ongoing clinical trials, including the ECHELON-1 Phase 3 trial in frontline HL, the ECHELON-2 Phase 3 trial in frontline mature T-cell lymphoma and the ALCANZA Phase 3 trial in CTCL. Opdivo is being evaluated either as monotherapy or in combination with other therapies in hematologic cancers, including multiple myeloma, chronic myelogenous leukemia, and Hodgkin and non-Hodgkin lymphomas including follicular and DLBCL. It has received Breakthrough Therapy designation for the treatment of patients with Hodgkin lymphoma who have failed treatment with autologous stem cell transplant and brentuximab vedotin.
SOURCE: Bristol-Myers Squibb press release