On February 20, 2025 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported data from Phase 2a trial of SLS009 (tambiciclib), a highly selective CDK9 inhibitor, in relapsed/refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL) (Press release, Sellas Life Sciences, FEB 20, 2025, View Source [SID1234650419]).

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The trial, conducted and funded by GenFleet Therapeutics (Shanghai), Inc. ("Genfleet"), was an open-label single-arm multicenter Phase 2a study in China evaluating SLS009 in combination with BTK inhibitor, Brukinsa (zanubrutinib) in r/r DLBCL. The results showed an overall response rate of 67%, more than double the expected overall response rate (ORR) of zanubrutinib alone. Among responders, one achieved complete response (CR), while three had partial response (PR) with target lesion shrinkages of 89%, 78%, and 56%, respectively. As of the last follow-up, after the median of 4.6 (range: 1.4 – 7.4) months follow-up, median overall survival (OS) was not reached, and six out of 9 patients were alive.

"These results represent a promising step forward in improving outcomes for DLBCL patients and underscores the potential of SLS009 in combination with zanubrutinib to deliver meaningful clinical benefits," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Achieving an ORR that significantly exceeds expectations, along with a complete response and multiple partial responses is a testament to the power of collaboration and innovation in tackling this challenging disease. We believe that the combination of SLS009 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 AML and spliceosome – chromatin mutations, including ASXL1 mutations."

Summary of Phase 2a data of SLS009 in DLBCL

Patients Characteristics

9 r/r DLBCL patients were enrolled: 3 with germinal center B-cell like (GCB) and 6 with activated B-cell like (ABC) subtype of DLBCL
ABC DLBCL, also known as non-GCB DLBCL, carries a worse prognosis vs. GCB DLBCL
The median age was 55 years old and the median of previous lines of therapy was 2 (range 2-4)
Efficacy and Safety

Among 6 non-GCB DLBCL (ABC DLBCL) patients, 4 had an objective response and one patient achieved stable disease (SD) for the disease control rate (DCR) of 5/6 (83%)
Overall response rate (ORR) was 4/6 (67%), more than double the expected ORR with zanubrutinib alone
One patient achieved complete response (CR), and three patients had partial response (PR) with target lesion shrinkages of 89%, 78%, and 56%, respectively
As of the last follow-up, after the median of 4.6 (range: 1.4 – 7.4) months follow-up, median overall survival (OS) was not reached
Six patients were alive as of the last follow-up, including 5 non-GCB DLBCL and 1 GCB DLBCL. Adverse events (AEs) grade ≥ 3 AEs were reported in 55.6% of patients, comparable to safety outcomes expected with Zanubrutinib alone
Genetic data of 6 out of 9 enrolled patients showed that none of the patients carried MYD88 or CD79B mutations predictive of better response to BTK inhibitors. The patient who achieved complete response (CR) by CT had MYC amplification, which is expected, but interestingly also harbored TP53 mutations, indicating that CDK9 inhibition with SLS009 could circumvent TP53 mutated cancers drug resistance.
"These additional data from yet another indication help us further expand the scope of SLS009," said Dragan Cicic, MD, Chief Development Officer of Sellas. "In parallel with our very advanced clinical development in acute myeloid leukemia, 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."