CG009301 for adults with relapsed or treatment‑resistant blood cancers

A Phase 1, Open-label, Multicentre Study Evaluating the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics, and Preliminary Efficacy of CG009301 for Injection in Adult Subjects With Relapsed or Refractory Haematological Malignancies

This trial will try a new drug called CG009301 to see if it's safe and helps adults whose leukemia or related blood cancers have come back or not responded to prior treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Cullgen (Shanghai),Inc (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 3 sites (Nanchang and 2 other locations)
• Trial ID: NCT07347171 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase 1 trial gives adults with relapsed or refractory hematologic malignancies escalating doses of CG009301 to determine the maximum tolerated dose and the objective best dose. The study has a dose-escalation stage open to various relapsed/refractory blood cancers and a dose-expansion stage focused on relapsed/refractory AML, high‑risk MDS, and relapsed/refractory ALL. Investigators will collect safety, tolerability, pharmacokinetic and pharmacodynamic data as well as preliminary signs of anti-tumor activity, and participants may continue treatment until disease progression. Results will be used to define dosing regimens for later trials.

Who should consider this trial

Good fit: Adults aged 18 to under 75 with relapsed or refractory hematologic malignancies who have failed standard therapies and for whom the investigator determines no acceptable standard treatment exists, with expansion cohorts specifically for R/R AML, high‑risk MDS, or R/R ALL.

Not a fit: Patients who are newly diagnosed, have non-hematologic cancers, significant comorbidities preventing experimental therapy, are younger than 18 or 75 and older, or who have effective standard treatment options are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, CG009301 could provide a new treatment option that controls disease in some adults with relapsed or refractory leukemia and related blood disorders.

How similar studies have performed: Early-phase trials of other GSPT1-targeting agents have shown preliminary signs of activity in AML but remain experimental with limited definitive success to date.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years and \<75 years at the time of signing the informed consent form; no gender restrictions;
2. Patients with relapsed/refractory haematological malignancies who have received a definitive diagnosis by pathology and/or cytology, confirmed histologically, and who have failed prior standard treatment regimens. The investigator must deem that no standard treatment is available or that the patient cannot tolerate existing therapies. Dose-escalation phase: unrestricted haematological tumour types. Dose-expansion phase: must meet one of the following criteria: a. Subjects meeting AML diagnostic criteria based on WHO 2022 5th edition classification, confirmed by bone marrow cytomorphology, including AML evolving from early-stage MDS or MPN. Criteria for recurrent AML: Leukaemic cells reappearing in peripheral blood after CR, or \>5% blast/immature cells in bone marrow, or extramedullary leukaemic infiltration. Criteria for refractory AML: - Treatment-naïve cases unresponsive to two standard-regimen cycles; - Relapse within 12 months after consolidation/intensification therapy following CR; - Relapse after 12 months unresponsive to conventional chemotherapy; Patients with two or more relapses; Persistent extramedullary leukaemia; b. Patients diagnosed with high-risk or very high-risk MDS according to the WHO 2022 5th edition classification, with a percentage of blasts in bone marrow smear or biopsy pathology \< 20%, and deemed by the investigator to have no other appropriate treatment options. Diagnostic criteria for recurrent MDS: Following achievement of complete remission, partial remission, or haematological improvement, at least one of the following must occur: - Bone marrow blastic count returns to pre-treatment levels; - ANC or PLT decreases by ≥50% from best response; - HGB decreases by ≥15 g/L or becomes transfusion-dependent. Diagnostic criteria for refractory MDS: Following adequate treatment (at least four cycles of demethylating agent therapy), meeting the IWG 2023 response criteria for "stable disease", "failure", or "disease progression"; progression after demethylating agent or other drug therapy, or patient intolerance to toxicity (e.g., treatment-related grade 3 or higher hepatic or renal toxicity during therapy leading to permanent discontinuation); c. Subjects meeting ALL diagnostic criteria based on WHO 2022 5th edition classification, with ≥20% primitive/immature lymphocytes in bone marrow. Relapsed ALL diagnostic criteria: Patients who, after achieving CR following induction therapy, exhibit recurrence of leukaemic cells in peripheral blood, \>5% primitive/immature lymphocytes in bone marrow, or development of extramedullary disease; Criteria for refractory ALL: Patients failing to achieve CR following standard induction therapy;
3. ECOG performance status score of 0-1;
4. Investigator-assessed expected survival ≥3 months;
5. Recovery of toxicities from prior treatment to ≤Grade 1 according to NCI-CTCAE v5.0 (excluding alopecia and long-term stable chronic conditions);
6. No prior autologous haematopoietic stem cell transplantation, or transplantation more than 2 months prior with toxicities resolved to ≤ Grade 1;
7. Adequate organ function support, with screening laboratory tests meeting all criteria: a. Coagulation function prior to study drug administration: INR ≤ 1.5 × ULN or aPTT ≤ 1.5 × ULN; b. Hepatic function: serum total bilirubin ≤ 2× ULN; AST and/or ALT ≤ 2.5× ULN; c. Cr ≤ 2× ULN or CrCL \> 30 mL/min (calculated using Cockcroft-Gault formula); d. LVEF ≥ 40%; and QTc ≤ 480 milliseconds; e. White blood cell count may decrease below 50.0 × 10⁹/L at baseline or following hydroxyurea administration
8. Non-pregnant and non-lactating: Infertile subjects; or subjects with potential for conception who agree to use effective contraception (hormonal, barrier, or abstinence). Male subjects must also abstain from sperm donation during study participation and for 90 days after the last dose of CG009301 injection. Women of childbearing potential must have a negative serum pregnancy test (serum-β-hCG) during the screening period;
9. Understand the study's purpose, process, nature, significance, potential benefits, and risks, and voluntarily sign the written informed consent form. Be able to comply with scheduled visits, treatment plans, laboratory tests, and other study instructions or procedures.

Exclusion Criteria:

1. Central nervous system leukaemia presenting with neurological and/or psychiatric symptoms;
2. Receipt of antitumour therapy (excluding hydroxyurea and prophylactic intrathecal injections) such as chemotherapy, immunotherapy, targeted therapy, or biological therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first study drug administration; receipt of radiotherapy within 2 weeks; receipt of traditional Chinese herbal medicine within 2 weeks;
3. Major surgery within 4 weeks prior to the first study dose, or anticipated need for major surgery during the study period;
4. Active infection deemed uncontrolled by the investigator following treatment with antibiotics, antiviral agents, or antifungal medications;
5. Severe or uncontrolled underlying medical conditions deemed ineligible for inclusion by the investigator, including but not limited to respiratory disorders (e.g., chronic obstructive pulmonary disease requiring oxygen therapy, moderate or higher asthma, moderate or higher pulmonary fibrosis, recurrent pulmonary oedema), cardiovascular disorders (e.g., prior coronary artery bypass grafting or coronary stent implantation, myocardial infarction within the past 6 months, NYHA Class III-IV heart failure), unstable angina within the past 6 months, uncontrolled hypertension (systolic \>160 mmHg or diastolic \>100 mmHg), arrhythmias requiring ongoing medical or interventional management), endocrine disorders (severe hyperthyroidism/hypothyroidism, uncontrolled diabetes mellitus), and neurological/psychiatric conditions affecting cognition, compliance, or personal safety (e.g., unstable epilepsy, dementia, schizophrenia, depression); psychiatric disorders (e.g., unstable epilepsy, dementia, schizophrenia, depression);
6. Active autoimmune diseases (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis), or allergy to the study drug or excipients;
7. Significant non-leukaemia-related bleeding risk (e.g., anticoagulant or antiplatelet therapy, arteriovenous malformation), or recent history of major bleeding (e.g., gastrointestinal haemorrhage, intracranial haemorrhage, disseminated intravascular coagulation);
8. Grade 2 or higher central nervous system or peripheral neuropathy (excluding stable Grade 3 conditions lasting over 6 months that do not impair daily functioning);
9. Allogeneic haematopoietic stem cell transplantation within 12 months prior to initial administration;
10. History of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolic event within 6 months prior to initial administration (thrombosis originating from implanted venous access ports or catheters, superficial vein thrombosis, or lacunar cerebral infarction are not considered "severe" thromboembolic events); Known familial and/or acquired thrombotic predisposition, such as hereditary or acquired defects in anticoagulant proteins, coagulation factors, fibrinolytic proteins, or presence of acquired risk factors conferring high thrombotic propensity;
11. HIV, HBV, and HCV infection: positive HIV antibody and PCR tests; HBsAg positive or viral DNA ≥100 IU/mL; positive HCV antibody with HCV-RNA quantification exceeding the upper limit of normal;
12. Individuals who received (attenuated) live virus vaccination within 4 weeks prior to first dosing;
13. Individuals with a documented history of alcohol or substance abuse;
14. Any past or current medical condition, treatment, or laboratory abnormality that may interfere with study results or affect the subject's ability to complete the study, or if the investigator deems the subject unsuitable for participation in this study.

Where this trial is running

Nanchang and 2 other locations

• The First Affiliated Hospital of Nanchang University — Nanchang, China (Recruiting)
• The Haematology Hospital of the Chinese Academy of Medical Sciences — Tianjin, China (Recruiting)
• Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology — Wuhan, China (Recruiting)

Study contacts

• Principal investigator: Jianxiang Wang, MS — The Haematology Hospital of the Chinese Academy of Medical Sciences
• Study coordinator: Xiangyu Jin, MS

Conditions Leukemia; AML; MDS; GSPT1; CG009301