Combining Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) with Seattle Genetics’ antibody-therapy conjugate Adcetris (brentuximab vedotin) has been shown to be effective and safe in people with recurrent Hodgkin’s lymphoma (HL). Based on these positive findings, the companies are planning a potentially pivotal Phase 3 clinical trial in these patients.
The randomized, open-label and global study, expected to begin this year, will compare a combination of Opdivo and Adcetris, and Adcetris as a stand-alone therapy, in patients with relapsed or refractory classical HL who are ineligible for an autologous stem cell transplant (ASCT) or failed after receiving ASCT.
This combination therapy is being evaluated in multiple, ongoing Phase 1/2 studies in patients with relapsed or refractory HL and CD30-positive relapsed or refractory non-HL — including T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell malignancies, like mediastinal B-cell lymphoma and mediastinal gray zone lymphoma.
In January, results from a Phase 1 study showed that all 10 patients with recurrent HL had a good response to the combo treatment, with 63 percent achieving complete responses. The therapy was also found to be well-tolerated, with manageable side effects. These results were presented at the 58th Annual Meeting & Exposition of the American Society of Hematology, Dec. 3–6, 2016.
The combination therapy is also being examined as a potential treatment for older HL patients and for children, adolescents and young adults with relapsed/refractory classical HL.
Opdivo (nivolumab) is an inhibitor of the programmed cell death (PD) 1 protein, a protein that plays an important role in down-regulating the immune system. By blocking PD-1, Opdivo releases this inhibition on immune cells, allowing them to more effectively attack tumor cells.
It was approved in 2016 by the U.S. Food and Drug Administration (FDA) to treat classical Hodgkin’s lymphoma (cHL) adult patients who relapsed or whose cancer had progressed after ASCT followed by Adcetris treatment.
Adcetris, approved by the FDA in 2011, is an antibody-drug conjugate directed to CD30, a defining marker of classical HL. It combines the targeting ability of a monoclonal antibody with the potency of a cell-killing agent.
“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,” Jonathan Drachman, MD, chief medical officer and executive vice president, research and development, at Seattle Genetics, said in a press release. “We are evaluating Adcetris in novel combinations in order to identify optimal treatment regimens for patients with CD30-expressing lymphomas.”
The combination of Adcetris and Opdivo is not yet approved for the treatment of relapsed/refractory HL.