On May 4, 2023 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 positive topline data for the cohort of patients with acute myeloid leukemia (AML) from its Phase 1 dose-escalation trial in relapsed/refractory (r/r) myeloid malignancies for GFH009, its CDK9 inhibitor (Press release, Sellas Life Sciences, MAY 4, 2023, View Source [SID1234631054]). Dose escalation continues in the lymphoma cohort with the last dose level of 75 mg weekly. Clinical activity observed in the lymphoma group will be announced after completion of the last dose level and is expected by the end of the second quarter or early third quarter of 2023.

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In the cohort of patients with AML, GFH009 treatment showed evidence of anti-tumor activity increasing with higher doses and no significant safety issues, including at the highest dose levels. The recommended Phase 2 dose (RP2D) for AML has been established and submitted to the U.S. Food and Drug Administration (FDA). SELLAS plans to commence a Phase 2a trial with GFH009 in combination with venetoclax and azacitidine (aza/ven) in patients with AML during the second quarter of 2023 with topline data expected by the end of the year.

"We are thrilled to share promising signs of safety and clinical activity for GFH009 that support advancement into the Phase 2 clinical study in patients with AML, in parallel to completing the Phase 1 lymphoma cohort dose escalation," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "These data include results from patients with difficult to treat advanced heavily pretreated blood cancers, which highlight the significant unmet need of patients that have failed current standards of care. The strength of the AML cohort data supports expediting our clinical strategy to initiate a Phase 2a trial in patients with AML during the second quarter of 2023."

The Phase 1 interim analysis included 72 patients in the AML (n = 31) and lymphoma (n = 41) cohorts who were high-risk, advanced, heavily pretreated and resistant to multiple prior therapies. In these difficult to treat cohorts of patients with advanced blood cancer, 94% of patients are alive to date (29/31 in AML cohort and 39/41 in lymphoma cohort) with one patient alive more than 18 months following the beginning of treatment. Two dosing regimens were tested in incremental GFH009 dose levels from 2.5 mg to 75 mg, either a twice a week (BIW) regimen or once a week (QW) regimen. No further dose escalations are planned in the AML cohort,

All key study objectives regarding pharmacokinetic (PK), pharmacodynamic (PD), safety and clinical activity data were met:

Efficacy: Anti-tumor activity and clinical responses across groups and dose levels were observed, indicating a broad therapeutic index. Meaningful cell killing activity was defined as ≥50% reduction in blasts in the bone marrow.
AML cohort: cell killing activity observed at the following dose levels:
9 mg BIW: 50.0% bone marrow blast (BMB) reduction;
15 mg BIW: 53.8% BMB reduction;
30 mg QW: 57.1% BMB reduction;
45 mg QW: 61.3% BMB reduction;
60 mg QW: 77.3% BMB reduction.
Durable complete remission (CR) with no minimal residual disease (MRD) in one patient with AML who had failed prior venetoclax plus azacytidine (aza/ven) therapy. The patient continues to be in CR 7 months following commencement of treatment. Historic, best available therapy median survival for patients relapsed after aza/ven is estimated at 2.5 months.
Safety: No dose limiting toxicities, no higher grade non-hematologic toxicities of any kind, some hematologic toxicities difficult to determine in patients with hematologic cancers but short in duration and reversible.
Pharmacokinetic (PK) Data: Achieved desired 24 hours > IC90 peripheral blood concentrations after the first infusion, with IC90 concentrations resulting in up to 97% cancer cell killed.
Pharmacodynamic (PD) Data: Achieved desired levels of MCL1 and MYC suppression in peripheral blood with decrease in MCL1 or MYC observed in 97% (66/68) of analyzed patients. A trend of proportionally increased maximum inhibition of MCL1 and MYC observed among higher doses (22.5 mg to 60 mg) in both AML and lymphoma patients, which is more prominent in QW cohorts compared to BIW cohorts. QW regimen was able to induce longer sustained inhibition (at least 6 hours) of MCL1 and MYC than BIW treatment, allowing longer period for CDK9 inhibition to induce cancer cell apoptosis.
"I am encouraged by the results from the Phase 1 GFH009 trial thus far," said Joshua Zeidner, MD, Associate Professor of Medicine, Chief of Leukemia Research, Associate Chief of Research in Division of Hematology, and Director of Clinical Cancer Research Commercial Integration at University of North Carolina Lineberger Comprehensive Cancer Center. "Novel agents are sorely needed in relapsed/refractory AML. I am looking forward to the next step of combining GFH009 with azacitidine and venetoclax where the mechanism of action of GFH009 is promising and has potential to add to our treatment armamentarium in AML."

The totality of the AML data will be presented at a major medical conference in Q4 2023 and the lymphoma topline data is expected by late second quarter/early third quarter 2023.