A phase 2a clinical trial conducted in China has revealed encouraging results for the combination therapy of tambiciclib (SLS009) and zanubrutinib (Brukinsa) in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The study demonstrated significant efficacy with a 67% overall response rate (ORR) among evaluable patients.
Among the six evaluable patients, one achieved a complete response (CR), while three others showed partial responses (PRs) with impressive target lesion shrinkages of 89%, 78%, and 56%. The trial's follow-up data at a median of 4.6 months showed promising survival outcomes, with six out of nine total patients still alive.
Strong Response in ABC DLBCL Subtype
The combination therapy showed particularly impressive results in patients with activated B-cell–like (ABC) DLBCL. Among six patients with this subtype, four responded to treatment and one maintained stable disease, resulting in an 83% disease control rate. These outcomes are especially noteworthy given the typically aggressive nature of ABC DLBCL.
Patient Demographics and Trial Design
The ongoing multicenter, open-label study enrolled patients aged 18 and above with various forms of relapsed/refractory DLBCL. The median age of participants was 55 years, with patients having received a median of 2 prior therapy lines (range: 2-4). Treatment consisted of tambiciclib administered at varying doses (75 mg, 60 mg, or 100 mg once weekly) combined with zanubrutinib at 160 mg twice daily.
Safety and Genetic Analysis
Safety monitoring revealed grade 3 or higher adverse effects in 55.6% of patients. Notably, genetic analysis of six evaluable patients showed no MYD88 or CD79B mutations, which are typically associated with better responses to BTK inhibitors. Interestingly, the patient achieving complete response carried both a MYC amplification and a TP53 mutation.
Expert Perspectives
Dr. Angelos Stergiou, President and CEO of SELLAS Life Sciences Group, emphasized the significance of these results: "These results represent a promising step forward in improving outcomes for DLBCL and underscores the potential of tambiciclib in combination with zanubrutinib to deliver meaningful clinical benefits."
Dr. Dragan Cicic, Chief Development Officer of Sellas, highlighted the broader implications: "These additional data from yet another indication help us further expand the scope of tambiciclib. We are continuously working on additional clinical and preclinical programs in other indications and uncovering genetic biomarkers that make all the difference in today's drug development."
