Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML
A Phase I/IIa, Open-Label Dose Escalation and Dose Expansion Study of Intravenous GFH009 Single Agent and in Combination With Venetoclax and Azacitidine in Patients With Relapsed/Refractory Hematologic Malignancies and High-Risk Newly Diagnosed AML
1 other identifier
interventional
160
2 countries
25
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2021
Longer than P75 for phase_1
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 28, 2020
CompletedFirst Posted
Study publicly available on registry
October 19, 2020
CompletedStudy Start
First participant enrolled
May 10, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
May 1, 2026
March 1, 2026
5.6 years
September 28, 2020
April 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Safety and Tolerability: Dose Limiting Toxicities (DLTs)
The incidence of DLTs
21 to 28 days
Safety and Tolerability: adverse events (AEs)
The incidence and severity of all AEs
approximately 2 years
Efficacy: ORR
Overall response rate is the proportion of patients showing anti-leukemic activity in response to treatment
2 years
Secondary Outcomes (9)
PK parameter AUC0-t
approximately 3 months
PK parameter AUC0-∞
approximately 3 months
Efficacy: DOR
2 years
Efficacy: PFS
2 years
Efficacy:OS
2 years
- +4 more secondary outcomes
Study Arms (11)
Group 1. Dose escalation in patients with r/r AML
EXPERIMENTALIn the dose escalation part, the dose levels will be escalated following the Bayesian optimal interval (BOIN) design. China study sites only. (Completed).
Group 2. Dose escalation in patients with r/r CLL/SLL or lymphoma
EXPERIMENTALIn the dose escalation part, the dose levels will be escalated following the Bayesian optimal interval (BOIN) design. China and US study sites. (Completed).
Group 3 Cohort 1. 45 mg QW in patients with r/r AML
EXPERIMENTALSLS009 (45 mg QW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed on or are refractory to venetoclax-based regimens. US study sites only. (Cohort completed)
Group 3 Cohort 2. 60 mg QW in patients with r/r AML.
EXPERIMENTALSLS009 (60 mg QW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed on or are refractory to venetoclax-based regimens. US study sites only. (Cohort completed).
Group 3 Cohort 3. 30 mg BIW in patients with r/r AML.
EXPERIMENTALSLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed on or are refractory to venetoclax-based regimens. US study sites only. (Cohort completed).
Group 3 Cohort 4. 30 mg BIW in patients with r/r AML with ASXL1 mutation.
EXPERIMENTALSLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed or are refractory to venetoclax-based regimens and with documented ASXL1 mutation.
Group 3 Cohort 5. 30 mg BIW in pts with r/rAML with other than ASXL1 mutations
EXPERIMENTALSLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed or are refractory to venetoclax-based regimens and with documented Defining somatic mutations, Cytogenetic abnormalities defining acute myeloid leukemia, myelodysplasia related, other than ASXL1 mutation per WHO 5th Edition classification.
Group 4 (treatment arm): SLS009, venetoclax, azacitidine
EXPERIMENTALSLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with newly diagnosed AML less likely to benefit from standard venetoclax and azacitidine therapy based on molecular profiling.
Group 4 (control arm): venetoclax and azacitidine
ACTIVE COMPARATORVenetoclax and azacitidine in patients with newly diagnosed AML less likely to benefit from standard venetoclax and azacitidine therapy based on molecular profiling.
Group 5 (treatment arm): SLS009, venetoclax, azacitidine (not yet recruiting)
EXPERIMENTALSLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with newly diagnosed AML. Patients who initiate treatment with venetoclax and azacitidine but demonstrate a confirmed lack of any response after two treatment cycles.
Group 5 (control arm): venetoclax and azacitidine (not yet recruiting)
ACTIVE COMPARATORVenetoclax and azacitidine in patients with newly diagnosed AML. Patients who initiate treatment with venetoclax and azacitidine but demonstrate a confirmed lack of any response after two treatment cycles.
Interventions
Solution for injection
Tablets
Solution for injection
Eligibility Criteria
You may qualify if:
- For Groups 1, 2, 3, 4 and 5:
- 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.
- Adequate hepatic function as evidenced by meeting all the following requirements:
- 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.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 ×ULN.
- Measured or calculated (determined by the Cockcroft-Gault equation) serum creatinine clearance (CrCl) ≥ 60 mL/min (glomerular filtration rate can be alternative to CrCl) for adult patients or serum creatinine ≤ 1.5 x ULN; or if serum creatinine \> 1.5 x ULN, then serum creatinine clearance (CrCl) ≥ 50 mL/min (estimated by Cockcroft-Gault formula or other appropriate formula) for pediatric patients. Whether the value is calculated by equation or measured directly can be based on institutional standard practice.
- Amylase ≤ 1.5 × ULN.
- Eastern cooperative oncology group (ECOG) performance status 0-2.
- The electrolytes and uric acid level need to be stable judged by investigators for at least 3 days before the first dose of GFH009 (Medical intervention is permitted).
- For AML and other leukemias:
- Peripheral WBC counts \< 50,000/µL. Cytoreduction prior to study will be allowed with hydroxyurea; hydroxyurea use will also be permitted during treatment period in patients with proliferative, progressive disease. Use of leukapheresis for the purpose of lowering WBC counts to make the patient eligible for enrolment is not permitted.
- Recovery to grade 0-1 from adverse events related to prior anti-tumor therapy except alopecia, fatigue, \< Grade 2 sensory neuropathy and endocrinopathies controlled with hormone replacement therapy.
- For women of childbearing potential, she must consent to use highly effective methods (e.g., total abstinence, placement of an intrauterine device) of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug if enrolled in Group 1 and 2, and 6 months enrolled in Group 3.
- +26 more criteria
You may not qualify if:
- For Groups 1, 2, 3, 4 and 5:
- 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.
- Severe cardiovascular disease within 6 months of study entry, including any of the following:
- 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.
- History/evidence of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting).
- Average QTcF ≥ 450 msec (males) or ≥ 470 msec (females) on screening ECG.
- Moderate or above regurgitation on echocardiogram
- Patients with prior treatment with cardiotoxic agents who have experienced drug induced cardiotoxicities during or after treatment, where cardiotoxic agents include but are not limited to anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxantrone); trastuzumab and trastuzumab based ADCs; tyrosine kinase inhibitors (sunitinib, imatinib); alkylating agents (cyclophosphamide).
- Patients who are on systemic antibiotics are eligible to participate as long as the antibiotics are not expected to have significant DDI with GFH009 (A list of approved concomitant medications will be provided to investigators. If any antibiotic is not included in the approved list, it can be discussed with the sponsor or designated CRO on a case-by-case basis).
- Active hepatitis B or hepatitis C virus infection. Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy have to be on a suppressive antiviral therapy prior to enrollment.
- Patients with HCV may be enrolled if the HCV is stable, and the patient is not at risk for hepatic decompensation.
- Patients with known HIV infection except if:
- They have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL, and
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
O'Neal Comprehensive Cancer Center, University of Alabama
Birmingham, Alabama, 35233, United States
City of Hope - Phoenix
Goodyear, Arizona, 85338, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
City of Hope - Atlanta
Newnan, Georgia, 30265, United States
City of Hope - Chicago
Zion, Illinois, 60099, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Clinical Research Alliance, Inc.
Lake Success, New York, 11042, United States
New York - Presbyterian Hospital
New York, New York, 10032, United States
UNC School of Medicine, Division of Hematology
Chapel Hill, North Carolina, 27599, United States
Bon Secours St. Francis Cancer Center
Greenville, South Carolina, 29607, United States
Baylor Scott & White Health
Dallas, Texas, 75246, United States
MD Anderson
Houston, Texas, 77091, United States
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, China
Anhui Provincial Hospital
Hefei, Anhui, China
Affiliated Cancer Hospital of Chongqing University
Chongqing, Chongqing Municipality, China
Cancer prevention and treatment center of Sun Yat sen University
Guangzhou, Guangdong, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Affiliated Hospital of Hebei University
Baoding, Hebei, China
Henan Cancer Hospital
Zhengzhou, Henan, 450000, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
The First Affiliated Hospital Of Nanchang University
Nanchang, Jiangxi, China
Shengjing Hospital Affiliated to China Medical University
Shenyang, Liaoning, China
Linyi Cancer Hospital
Linyi, Shandong, China
Blood disease hospital, Chinese Academy of Medical Science
Tianjin, Tianjin Municipality, 300000, China
The Second Affiliated hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Dragan Cicic, MD
SELLAS Life Sciences Group, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 28, 2020
First Posted
October 19, 2020
Study Start
May 10, 2021
Primary Completion (Estimated)
December 30, 2026
Study Completion (Estimated)
December 31, 2027
Last Updated
May 1, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share