SLS009 (formerly GFH009) is a potent and highly selective CDK9 inhibitor. In this study the safety, tolerability, and antitumor activity of single agent SLS009 are assessed in two dose escalation groups (Group 1 in patients with relapsed/refractory AML, Group 2 in patients with relapse/refractory lymphoma/CLL/SLL). The safety, tolerability, and antitumor activity of SLS009 in combination with venetoclax and azacitidine in patient with relapsed/refractory AML who have relapsed on or are refractory to venetoclax-based regimens are being assessed in five cohorts of the expansion Group 3. Groups 4 and 5 have been added to evaluate efficacy, safety, and tolerability of GFH009 in combination with venetoclax and azacitidine in newly diagnosed AML patients who are less likely to benefit from standard induction treatment with venetoclax plus HMA only regimens.
Male or female ≥ 18 years. For Group 3 Cohorts 4 and 5 only male or female ≥18 years and pediatric patients 12-18 years and ≥40 kg body mass
Written informed consent must be obtained prior to any screening procedures
For AML, acute promyelocytic leukemia (APL) patients are not included in the study.
Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubin is < 1.5 × ULN.
Uncontrolled medical conditions such as hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg), a history of hypertensive crisis, or a history of hypertensive encephalopathy.
History of previous exposure to any other CDK9 inhibitors.
Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study.
Clinically significant heart disease such as congestive heart failure requiring treatment (NYHA class III or IV), left ventricular ejection fraction (LVEF) < 50% as determined by MUGA scan or echocardiogram (ECHO), (if only with historical occasional low LVEF but without any symptoms or relevant medical history, and the LVEF at screening is > 50%, the subject is eligible), or clinically significant arrythmia.
Sequential
SLS009
DrugSolution for injection
venetoclax
DrugTablets
azacitidine
DrugSolution for injection
11
Treatment groupsSee each treatment group below.
Safety and Tolerability: Dose Limiting Toxicities (DLTs)
The incidence of DLTs
Safety and Tolerability: adverse events (AEs)
The incidence and severity of all AEs
Efficacy: ORR
Overall response rate is the proportion of patients showing anti-leukemic activity in response to treatment
PK parameter AUC0-t
Area under the plasma concentration-time curve (from zero to the time of the last measurable concentration)
PK parameter AUC0-∞
Area under the plasma concentration-time curve (from zero to infinity)
Efficacy: DOR
Duration of response in patients
Efficacy: PFS
Progression-free survival
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