Bristol-Myers Squibb Company and Seattle Genetics, Inc. announced that the companies have entered into a collaboration agreement to evaluate the combination of Bristol-Myers Squibb’s immunotherapy Opdivo and Seattle Genetics’ antibody-drug conjugate (ADC) Adcetris in a pivotal phase 3 clinical trial. The trial will evaluate the combination of Adcetris and Opdivo versus Adcetris alone as a potential treatment option for patients with relapsed/refractory or transplant-ineligible advanced classical Hodgkin lymphoma (HL). The combination of Adcetris and Opdivo is not approved for the treatment of relapsed/refractory HL.

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 and other immune cells.

“Adcetris was approved by the FDA in 2011 as the first new therapeutic option for patients with Hodgkin lymphoma in more than 30 years. Adcetris has now become the standard of care for relapsed Hodgkin lymphoma, with more than 20,000 patients treated,” said Jonathan Drachman, M.D., chief medical officer and executive vice president, research and development of Seattle Genetics. “We are evaluating Adcetris in novel combinations in order to identify optimal treatment regimens for patients with CD30-expressing lymphomas. We are pleased to expand this collaboration with Bristol-Myers Squibb to evaluate Adcetris compared to the combination of Adcetris and Opdivo in a pivotal phase 3 study in relapsed Hodgkin lymphoma.”

“Clinical collaborations enable our pursuit of innovative combinations of therapies that may offer the potential of improved outcomes for patients with difficult to treat cancers,” said Fouad Namouni, M.D., head of oncology development, Bristol-Myers Squibb. “Our collaboration with Seattle Genetics combines our experience and understanding of Hodgkin lymphoma and a shared goal of providing patients with additional treatment options. We look forward to initiating our registrational study of Adcetris and Opdivo in patients with relapsed Hodgkin lymphoma.”

The planned phase 3 study will be a randomized, open-label global clinical trial in classical HL patients with relapsed/refractory disease who are ineligible for autologous stem cell transplant (ASCT) or after failure of ASCT. Participants will be randomized to receive treatment with either Adcetris in combination with Opdivo or Adcetris alone. The pivotal study is expected to begin in mid-2017.

In addition to the planned pivotal trial, Adcetris and Opdivo are being evaluated as combination therapy in multiple ongoing phase 1/2 clinical trials. These include studies in patients with relapsed or refractory Hodgkin lymphoma and CD30-expressing relapsed or refractory non-Hodgkin lymphomas, including T-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell malignancies, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. In addition, the Adcetris and Opdivo combination is being evaluated for older HL patients and relapsed/refractory classical HL for children, adolescents and young adults.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and  Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

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), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

Seattle Genetics and Takeda are jointly developing Adcetris. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize Adcetris in the rest of the world. Adcetris has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory HL and systemic anaplastic large cell lymphoma (sALCL). In addition, Adcetris is being evaluated broadly in more than 70 ongoing clinical trials, including three phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma for which a supplemental Biologics License Application is planned in mid- 2017. See important safety information below.

Opdivo (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

Opdivo (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Opdivo (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Opdivo.

Opdivo (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

Opdivo (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Opdivo (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

Opdivo (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumour response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.