SELLAS Announces Positive Data from Phase 2a Trial of SLS009 in Combination with Zanubrutinib in DLBCL
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.
SELLAS Life Sciences Group (NASDAQ: SLS) ha annunciato risultati positivi da uno studio di fase 2a di SLS009 (tambiciclib) combinato con zanubrutinib in pazienti con Linfoma Diffuso a Grande Cellula B (r/r DLBCL) in recidiva/rifrangente. Lo studio, condotto da GenFleet Therapeutics in Cina, ha mostrato un 67% di tasso di risposta globale, più del doppio rispetto a quello di zanubrutinib da solo.
Tra i 9 pazienti arruolati, uno ha raggiunto una risposta completa, mentre tre hanno avuto risposte parziali con riduzioni delle lesioni target del 89%, 78% e 56%. Dopo un follow-up mediano di 4,6 mesi, il 67% dei pazienti era ancora vivo. Nel sottogruppo di DLBCL non-GCB, il tasso di controllo della malattia ha raggiunto l'83%. Eventi avversi di grado ≥ 3 sono stati riportati nel 55,6% dei pazienti, paragonabili al profilo di sicurezza di zanubrutinib. È interessante notare che l'analisi genetica ha rivelato che il paziente con risposta completa presentava amplificazione di MYC e mutazioni di TP53, suggerendo che SLS009 potrebbe potenzialmente superare la resistenza ai farmaci nei tumori con mutazioni TP53.
SELLAS Life Sciences Group (NASDAQ: SLS) anunció resultados positivos de un ensayo de fase 2a de SLS009 (tambiciclib) combinado con zanubrutinib en linfoma difuso de células B grandes en recaída/refractario (r/r DLBCL). El ensayo, realizado por GenFleet Therapeutics en China, mostró una tasa de respuesta global del 67%, más del doble que la de zanubrutinib solo.
Entre los 9 pacientes inscritos, uno logró una respuesta completa, mientras que tres tuvieron respuestas parciales con reducciones de las lesiones objetivo del 89%, 78% y 56%. Después de un seguimiento mediano de 4,6 meses, el 67% de los pacientes seguía con vida. En el subgrupo de DLBCL no-GCB, la tasa de control de la enfermedad alcanzó el 83%. Se informaron eventos adversos de grado ≥ 3 en el 55,6% de los pacientes, comparable al perfil de seguridad de zanubrutinib. Cabe destacar que el análisis genético reveló que el paciente con respuesta completa tenía amplificación de MYC y mutaciones de TP53, lo que sugiere que SLS009 podría superar potencialmente la resistencia a medicamentos en cánceres con mutaciones de TP53.
SELLAS Life Sciences Group (NASDAQ: SLS)는 재발/불응성 미만성 대세포 B 림프종(r/r DLBCL)에서 SLS009 (탐비시클립)과 자누브루틴을 병용한 2a상 시험의 긍정적인 결과를 발표했습니다. 중국의 GenFleet Therapeutics가 수행한 이 시험은 67%의 전반적인 반응률을 보였으며, 이는 자누브루틴 단독의 두 배 이상입니다.
등록된 9명의 환자 중 1명이 완전 반응을 보였고, 3명은 각각 89%, 78%, 56%의 목표 병변 크기 감소를 보이며 부분 반응을 보였습니다. 4.6개월의 중간 추적 관찰 후, 67%의 환자가 생존했습니다. 비-GCB DLBCL 하위 그룹에서 질병 조절률은 83%에 달했습니다. 3등급 이상의 부작용은 55.6%의 환자에게서 보고되었으며, 이는 자누브루틴의 안전성 프로필과 유사합니다. 특히, 유전자 분석 결과 완전 반응을 보인 환자가 MYC 증폭 및 TP53 돌연변이를 가지고 있어 SLS009가 TP53 돌연변이가 있는 암의 약물 저항성을 극복할 가능성이 있음을 시사합니다.
SELLAS Life Sciences Group (NASDAQ: SLS) a annoncé des résultats positifs d'un essai de phase 2a de SLS009 (tambiciclib) associé au zanubrutinib chez des patients atteints de lymphome diffus à grandes cellules B en rechute/réfractaire (r/r DLBCL). L'essai, réalisé par GenFleet Therapeutics en Chine, a montré un taux de réponse global de 67%, plus du double de celui du zanubrutinib seul.
Parmi les 9 patients inscrits, un a obtenu une réponse complète, tandis que trois ont eu des réponses partielles avec des réductions des lésions cibles de 89%, 78% et 56%. Après un suivi médian de 4,6 mois, 67% des patients étaient encore en vie. Dans le sous-groupe DLBCL non-GCB, le taux de contrôle de la maladie a atteint 83%. Des événements indésirables de grade ≥ 3 ont été signalés chez 55,6% des patients, ce qui est comparable au profil de sécurité du zanubrutinib. Il convient de noter qu'une analyse génétique a révélé que le patient ayant obtenu une réponse complète présentait une amplification de MYC et des mutations de TP53, ce qui suggère que SLS009 pourrait potentiellement surmonter la résistance aux médicaments dans les cancers présentant des mutations de TP53.
SELLAS Life Sciences Group (NASDAQ: SLS) gab positive Ergebnisse aus einer Phase 2a-Studie zu SLS009 (Tambiciclib) bekannt, das in Kombination mit Zanubrutinib bei rezidivierten/refraktären diffusen großzelligen B-Zell-Lymphomen (r/r DLBCL) getestet wurde. Die Studie, die von GenFleet Therapeutics in China durchgeführt wurde, zeigte eine 67% Gesamtansprechrate, mehr als doppelt so hoch wie die von Zanubrutinib allein.
Von den 9 eingeschlossenen Patienten erreichte einer eine komplette Ansprechrate, während drei eine partielle Ansprechrate mit Zielgeschwulstverkleinerungen von 89%, 78% und 56% hatten. Nach einer medianen Nachbeobachtungszeit von 4,6 Monaten waren 67% der Patienten noch am Leben. In der nicht-GCB DLBCL-Untergruppe erreichte die Krankheitskontrollrate 83%. Grad ≥ 3 unerwünschte Ereignisse wurden bei 55,6% der Patienten berichtet, was mit dem Sicherheitsprofil von Zanubrutinib vergleichbar ist. Bemerkenswert ist, dass die genetische Analyse ergab, dass der Patient mit kompletter Ansprechrate eine MYC-Amplifikation und TP53-Mutationen hatte, was darauf hindeutet, dass SLS009 möglicherweise die Medikamentenresistenz bei TP53-mutierten Krebserkrankungen überwinden könnte.
- 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
- 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
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
- Median Overall Survival Not Reached Yet –
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
“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% , and56% , 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?
How effective was SLS009 in treating non-GCB DLBCL patients?
What was the survival rate in the SLS009 Phase 2a trial?
What were the safety findings for SLS009 in the Phase 2a DLBCL trial?
How did SLS009 perform in patients with TP53 mutations?
