SELLAS Announces Positive Data from Phase 2a Trial of SLS009 in Combination with Zanubrutinib in DLBCL

Rhea-AI Summary

SELLAS Life Sciences Group (NASDAQ: SLS) announced positive results from a Phase 2a trial of SLS009 (tambiciclib) combined with zanubrutinib in relapsed/refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL). The trial, conducted by GenFleet Therapeutics in China, showed a 67% overall response rate, more than double that of zanubrutinib alone.

Among the 9 enrolled patients, one achieved complete response, while three had partial responses with target lesion shrinkages of 89%, 78%, and 56%. After a median follow-up of 4.6 months, 67% of patients remained alive. In the non-GCB DLBCL subgroup, the disease control rate reached 83%. Grade ≥ 3 adverse events were reported in 55.6% of patients, comparable to zanubrutinib's safety profile. Notably, genetic analysis revealed the complete response patient had MYC amplification and TP53 mutations, suggesting SLS009 could potentially overcome TP53-mutated cancer drug resistance.

Positive

• 67% overall response rate, more than double the expected rate with zanubrutinib alone
• 83% disease control rate in difficult-to-treat non-GCB DLBCL patients
• 67% survival rate after median 4.6 months follow-up
• Complete response achieved in one patient despite challenging TP53 mutations

Negative

• Grade ≥ 3 adverse events reported in 55.6% of patients
• Small patient sample size (only 9 patients)
• Relatively short follow-up period (median 4.6 months)

Insights

Clinical Trial Analyst

The Phase 2a trial results for SLS009 represent a significant breakthrough in DLBCL treatment, particularly for difficult-to-treat non-GCB subtypes. The 67% overall response rate achieved in combination with zanubrutinib is remarkable, especially considering it more than doubles the efficacy of zanubrutinib monotherapy. The 83% disease control rate in non-GCB DLBCL patients is particularly noteworthy given the traditionally poor prognosis for this subtype.

The efficacy demonstrated in patients with TP53 mutations is a important differentiator, as these mutations typically confer drug resistance and limit treatment options. This suggests SLS009's potential broader applicability in treating resistant cancers, significantly expanding its market opportunity. The safety profile, comparable to zanubrutinib monotherapy, indicates a manageable risk-benefit ratio that could facilitate regulatory approval.

However, investors should note that while these results are promising, SELLAS is strategically focusing on AML and spliceosome-chromatin mutations, with GenFleet leading future DLBCL development. This strategic decision allows SELLAS to optimize resource allocation while maintaining exposure to multiple potential revenue streams through partnership arrangements. The ability to demonstrate efficacy across different indications strengthens SLS009's value proposition and could attract additional partnership opportunities.

The genetic biomarker data, particularly the response in patients without MYD88 or CD79B mutations, suggests potential applications in patient populations that typically respond poorly to existing treatments. This could position SLS009 as a valuable option in precision medicine approaches, potentially commanding premium pricing in specific patient segments.

- Combination Achieved a 67% of Overall Response Rate, More than Double that of Zanubrutinib Alone; 83% Disease Control Rate in Difficult-to-Treat Non-GCB DLBCL (ABC DLBCL) Patients -

- Median Overall Survival Not Reached Yet – 67% of Patients Still Alive -

NEW YORK, Feb. 20, 2025 (GLOBE NEWSWIRE) -- 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, today announced data from Phase 2a trial of SLS009 (tambiciclib), a highly selective CDK9 inhibitor, in relapsed/refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL).

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.”

About SELLAS Life Sciences Group, Inc.

SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, GPS, is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has the potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing SLS009 (formerly GFH009) - potentially the first and best-in-class differentiated small molecule CDK9 inhibitor with reduced toxicity and increased potency compared to other CDK9 inhibitors. Data suggests that SLS009 demonstrated a high response rate in AML patients with unfavorable prognostic factors including ASXL1 mutation, commonly associated with poor prognosis in various myeloid diseases. For more information on SELLAS, please visit www.sellaslifesciences.com.

Forward-Looking Statements

This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as “plan,” “expect,” “anticipate,” “may,” “might,” “will,” “should,” “project,” “believe,” “estimate,” “predict,” “potential,” “intend,” or “continue” and other words or terms of similar meaning. These statements include, without limitation, statements related to the GPS clinical development program, including the REGAL study and the timing of future milestones related thereto. These forward-looking statements are based on current plans, objectives, estimates, expectations, and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties with oncology product development and clinical success thereof, the uncertainty of regulatory approval, and other risks and uncertainties affecting SELLAS and its development programs as set forth under the caption “Risk Factors” in SELLAS’ Annual Report on Form 10-K filed on March 28, 2024 and in its other SEC filings. Other risks and uncertainties of which SELLAS is not currently aware may also affect SELLAS’ forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. SELLAS undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations, or other circumstances that exist after the date as of which the forward-looking statements were made.

Investor Contact
Bruce Mackle
Managing Director
LifeSci Advisors, LLC
SELLAS@lifesciadvisors.com

Media Contact
Michael Fitzhugh
LifeSci Communications
mfitzhugh@lifescicomms.com

FAQ

What were the key results of SELLAS's Phase 2a trial for SLS009 in DLBCL?

The trial showed a 67% overall response rate when SLS009 was combined with zanubrutinib, more than double the expected rate of zanubrutinib alone. One patient achieved complete response, and three had partial responses with significant tumor shrinkage.

How effective was SLS009 in treating non-GCB DLBCL patients?

In non-GCB DLBCL patients, the combination therapy achieved an 83% disease control rate, with 4 out of 6 patients showing objective response and one patient achieving stable disease.

What was the survival rate in the SLS009 Phase 2a trial?

After a median follow-up of 4.6 months, 67% of patients (6 out of 9) were still alive, with median overall survival not yet reached.

What were the safety findings for SLS009 in the Phase 2a DLBCL trial?

Grade 3 or higher adverse events were reported in 55.6% of patients, which was comparable to the expected safety profile of zanubrutinib alone.

How did SLS009 perform in patients with TP53 mutations?

The trial showed promising results with one patient achieving complete response despite having TP53 mutations, suggesting SLS009 could potentially overcome TP53-mutated cancer drug resistance.