Tambiciclib Plus Zanubrutinib Delivers Responses in R/R DLBCL

Treatment with the combination of tambiciclib (SLS009) and zanubrutinib (Brukinsa) generated responses in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to data from a phase 2a trial (NCT06375733) conducted in China.1

Findings showed that evaluable patients treated with the combination (n = 6) experienced an overall response rate (ORR) of 67%, including 1 patient who achieved a complete response (CR). Three patients had partial responses (PRs) with respective target lesion shrinkages of 89%, 78%, and 56%.

At a median follow-up of 4.6 months (range, 1.4-7.4) for 9 total patients, the median overall survival was not reached, and 6 of the 9 patients were still alive. Among patients with activated B-cell–like (ABC) DLBCL (n = 6), 4 patients responded and 1 had stable disease, translating to a disease control rate of 83%.

“These results represent a promising step forward in improving outcomes for [patients with] DLBCL and underscores the potential of [tambiciclib] in combination with zanubrutinib to deliver meaningful clinical benefits,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS Life Sciences Group, stated in a news release. “Achieving an ORR that significantly exceeds expectations, along with a CR response and multiple PRs is a testament to the power of collaboration and innovation in tackling this challenging disease. We believe that the combination of [tambiciclib] and zanubrutinib demonstrates a synergy that could pave the way for more effective treatment options. Moving forward, GenFleet will determine the next steps regarding the trial’s continuation around lymphoma as SELLAS’ focus remains in acute myeloid leukemia and spliceosome – chromatin mutations, including ASXL1 mutations.”

The ongoing multicenter, open-label, nonrandomized, single-arm phase 1/2 study is enrolling patients at least 18 years of age with relapsed/refractory DLBCL including DLBCL not otherwise specified, T-cell/histiocyte-rich LBCL, high-grade B-cell lymphoma, or LBCL transformed from indolent B-cell lymphoma.2 Patients need to have disease that was relapsed or refractory following 2 to 4 prior lines of therapy that included an anthracycline and rituximab (Rituxan). Other key inclusion criteria consist of at least 1 measurable lesion; unsuitability to undergo stem cell transplant; an ECOG performance status of 0 to 2; and adequate organ function.

Patients are excluded if they have primary or secondary central nervous system lymphoma; have primary resistance to CDK9 or BTK inhibitors; or have a history of organ transplantation or allogeneic stem cell transplantation.

In the phase 1 portion of the study, patients received tambiciclib at 75 mg, 60 mg, or 100 mg once per week in combination with 160 mg of zanubrutinib twice per day until disease progression. In phase 2, tambiciclib is being given at the recommended phase 2 dose identified in phase 1 along with the same zanubrutinib regimen.

ORR is the primary end point of phase 2.

Among the 9 patients enrolled and treated thus far in the phase 2 portion of the study, 6 had ABC DLBCL, and 3 had germinal center B-cell–like DLBCL.1 Patients had a median age of 55 years and received a median of 2 prior lines of therapy (range, 2-4).

Safety data showed that grade 3 or higher adverse effects occurred in 55.6% of patients.

A genetic analysis showed that no evaluable patients (n = 6) harbored MYD88 or CD79B mutations, which could be predictive of improved response to BTK inhibitors. The patient who achieved a CR harbored a MYC amplification and a TP53 mutation.

“These additional data from yet another indication help us further expand the scope of [tambiciclib],” Dragan Cicic, MD, chief development officer of Sellas, added in a news release. “In parallel with our very advanced clinical development in AML, 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.”

References

1. SELLAS announces positive data from phase 2a trial of SLS009 in combination with zanubrutinib in DLBCL. News release. SELLAS Life Sciences Group. February 20, 2025. Accessed February 20, 2025. https://ir.sellaslifesciences.com/news/News-Details/2025/SELLAS-Announces-Positive-Data-from-Phase-2a-Trial-of-SLS009-in-Combination-with-Zanubrutinib-in-DLBCL/default.aspx
2. A study of GFH009 in combination with zanubrutinib in subjects with relapsed or refractory DLBCL. ClinicalTrials.gov. Updated December 13, 2024. Accessed February 20, 2025. https://clinicaltrials.gov/study/NCT06375733