Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1369-1369
• Main Authors: Flinn, Ian W., Friedman, Judah, Ho, Linda, Lee, Hun Ju
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-152231

Background Brentuximab vedotin (BV) is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody, a protease-cleavable linker, and the microtubule-disrupting agent, monomethyl auristatin E (MMAE). Direct cytotoxicity, driven by MMAE, is at the heart of the multifaceted anticancer activity of BV (Sutherland 2006). BV was the first ADC to be approved in multiple cancer types, including treatment-naïve Stage III or IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) (Connors 2017). Nivolumab is a fully humanized monoclonal antibody that targets programmed cell death protein 1 and is approved for the treatment of adults with relapsed/refractory (R/R) cHL. Both agents have been well tolerated with encouraging activity when combined with multi-agent chemotherapy. BV plus nivolumab was evaluated as a frontline treatment option for patients with cHL who are ≥60 years of age and ineligible for, or declined, conventional combination chemotherapy. The ongoing study reported an objective response rate (ORR) of 82% in 11 evaluable patients, and BV appears to be well tolerated in this population (Friedberg 2018). The combination of BV and nivolumab produced a 67% complete response (CR) rate and an estimated 3-year progression-free survival (PFS) rate of 77% in 93 patients with R/R cHL treated in the first-line salvage setting (Advani 2021). BV plus doxorubicin and dacarbazine (AD) without radiation therapy was evaluated in 34 patients with non-bulky Stage I or II cHL. BV-AD treatment resulted in interim and end of treatment (EOT) CR rates of 94% and 97%, respectively. The 4-year PFS and overall survival (OS) estimates were 91% and 100%, respectively. Peripheral sensory neuropathy (PSN) was low grade and only 1 patient had persistent PSN at the last follow-up (Abramson 2021). Part C of this study will evaluate BV, nivolumab, doxorubicin, and dacarbazine (AN+AD) in patients with Stage I or II cHL without bulky disease, a patient population similar to that studied in Abramson 2021. Based on the results of the trials summarized above, it is reasonable to expect that the combination of AN+AD will result in high response rates and be well tolerated, with potentially less toxicity compared with A+AVD. Study Design and Methods SGN35-027 (NCT03646123) is an open-label, multiple part, multicenter, phase 2 clinical trial of BV in patients with Stage III or IV cHL evaluating the efficacy and safety of A+AVD