ASH: I/O drugs pushing into blood cancers
- A preliminary peek at Phase 1/2 data from the combo of Seattle Genetics' Adcetris (brentuximab vedotin) and Bristol-Myers Squibb's Opdivo (nivolumab) in relapsed or refractory classical Hodgkin lymphoma (cHL) showed early signs of activity, though with increased levels of infusion-related reactions.
- Of 29 patients who could be evaluated, 26 (90%) had an objective response. The results were presented Monday at the annual American Society of Hematology (ASH) meeting.
- Merck & Co. also updated the results of KEYNOTE-087 and KEYNOTE-013, which looked at Keytruda (pembrolizumab) in relapsed or refractory cHL. The two trials had an ORR of 69% and 58% respectively. At a mean follow up of 29 months in the KEYNOTE-013 study, over 70% of patients had responses of 12 months or more.
After successes in solid tumors for Opdivo and Keytruda, both Bristol-Myers Squibb and Merck are looking to exploit hematological cancer indications to access the still growing immuno-oncology market. I/O drugs could be worth $30 billion by 2022, reports BioPharm Insight in a December 2016 report. Opdivo is predicted to contribute $12 billion of the total, outstripping Keytruda at $7.7 billion.
Relapsed or refractory classical Hodgkin lymphoma, which does not respond to standard chemotherapy or autologous stem cell transplantation, is difficult to treat. Opdivo got the nod from the EU last month for relapsed/refractory cHL post ASCT and post-Adcetris (brentuximab vedotin), making it the first PD-1/PD-L1 inhibitor to reach the blood cancer market. Adcetris is an antibody drug conjugate meant to boost the effectiveness of immunology drugs.
The combination data for the PD-1 antibody Opdivo and the antibody-drug conjugate Adcetris shows a 90% response rate, but this is in a Phase 1/2 trial with a small number of patients. However, it does show potential for an approach combining targeted and I/O therapy without traditional chemotherapy. The collaboration between Bristol-Myers Squibb and Seattle Genetics, signed in May 2015, is ongoing. This was created to evaluate the combination of the two drugs in two Phase 1/2 clinical trials; the first in relapsed or refractory cHL and the second trial in relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL).
"We are evaluating Adcetris broadly as the foundation of care for CD30-expressing lymphomas, including combination strategies that have the potential to improve efficacy," said Jonathan Drachman, CMO and EVP of R&D at Seattle Genetics. "We look forward to further evaluation of this innovative combination regimen in other disease settings, including frontline older HL patients and CD30-expressing non-Hodgkin lymphoma, in partnership with Bristol-Myers Squibb."
Merck is carrying out monotherapy and combination regimens based on Keytruda in hematological malignancies, with almost 40 studies underway, including trials designed to produce data for regulatory submissions.
- Bristol-Myers Squibb Statement
- Merck Statement
- BioPharma Dive ADCs: A booming field for new cancer-fighting therapies
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