Seattle Genetics and Bristol-Myers Squibb Company have entered into a clinical trial collaboration agreement to evaluate the investigational combination of Seattle Genetics’ antibody-drug conjugate (ADC) Adcetris (brentuximab vedotin) and Bristol-Myers Squibb’s immunotherapy Opdivo (nivolumab) in two planned phase 1/2 clinical trials. The first trial will evaluate the combination of Adcetris and Opdivo as a potential treatment option for patients with relapsed or refractory Hodgkin lymphoma (HL), and the second trial will focus on patients with relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL).
Adcetris is an ADC directed to CD30, a defining marker of classical HL, which combines the targeting ability of a monoclonal antibody with the potency of a cell-killing agent. 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 collaboration will expand our broad Adcetris clinical development program towards our goal of improving outcomes for patients with Hodgkin lymphoma and other CD30-expressing malignancies,” said Clay B. Siegall, president and chief executive officer of Seattle Genetics. “Ultimately, our vision is to advance the treatment of cancer by exploring more targeted treatment approaches that result in enhanced activity, reduced toxicities and improved long-term results for patients. We look forward to working with Bristol-Myers Squibb to define the activity and tolerability of adding Opdivo to Adcetris, and informing this potential treatment strategy in hematologic malignancies.”
“Bristol-Myers Squibb continues to strengthen its broad development programme for Opdivo through collaborations that explore novel combination regimens in areas of serious unmet need,” said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. “We are pleased to collaborate with Seattle Genetics on clinical research focussed on hematologic malignancies.”
The studies are expected to begin in 2015, with Seattle Genetics conducting the HL trial and Bristol-Myers Squibb conducting the NHL trial. Additional details of the collaboration were not disclosed.
Adcetris is approved in relapsed HL and systemic anaplastic large cell lymphoma (ALCL) but is not currently approved for the treatment of relapsed, transplant eligible HL or for the treatment of other types of NHL. Opdivo is currently not approved for the treatment of lymphoma.
Adcetris is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilising Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalisation into CD30-expressing tumour cells.
Seattle Genetics and Takeda are jointly developing Adcetris. Under the terms of the collaboration agreement, Seattle Genetics has US and Canadian commercialisation rights and Takeda has rights to commercialise Adcetris in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for Adcetris on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs. Adcetris has received marketing authorisation by regulatory authorities in more than 45 countries. In addition, Adcetris is being evaluated as an investigational agent in more than 30 ongoing clinical trials, including four phase 3 studies, across a variety of CD30-expressing malignances including HL.
The US 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 tumour 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 programme to study Opdivo in multiple tumour 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. The FDA granted Opdivo Breakthrough Therapy Designation in May 2014 for the treatment of patients with HL after failure of autologous stem cell transplant and brentuximab vedotin.
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: HL and NHL. NHL is further categorised into indolent (low-grade) or aggressive, including DLBCL. DLBCL is the most common type of NHL. HL is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30.