This study is a first-in-human (FIH) study which is required to understand the safety, tolerability, pharmacokinetics and preliminary efficacy of RJK-RT2831 injection in patients with hematologic malignancies
1. A male or female aged ≥ 18 and <75 years old.
2. The following three points are evaluated by the investigator and are deemed suitable to participate in the study: a) The subject fully understands the requirements of this study and voluntarily signs a written informed consent form; b) Be able to comply with the medication requirements of this study as well as all study related procedures and assessments; c) Not deemed as potentially unreliable and/or uncooperative.
3. An ECOG physical status score is ≤ 2 and an expected survival is ≥ 3 months.
4. Relapsed or refractory acute myeloid leukemia (AML) that meets the following criteria will be included in Phase Ⅰa : Patients diagnosed with AML according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours: -Myeloid and Histiocytic/Dendritic Neoplasms (Khoury et al., 2022), including any subtype except for acute promyelocytic leukemia (APL). These patients must have received at least one previous treatment and have failed to current standard treatments that provide clinical benefit.
1. APL is suspected or confirmed based on morphology, immunophenotyping, molecular testing, or chromosomal karyotyping, or other hematological tumors, such as myeloid sarcoma, mixed phenotype acute leukemia, accelerated phase and blast phase of chronic myeloid leukemia, etc.;
Received cytotoxic chemotherapy (except hydroxyurea use for subjects with leukocytosis >10,000 cells/mm3 or rapid disease progression), radiotherapy (except local palliative radiotherapy), immunotherapy, targeted therapy and other anti-tumor treatments within 14 days;
Received adoptive cell therapy, such as autologous or donor natural killer cell or T lymphocyte infusions (e.g., chimeric antigen receptor-T cells), unless > 60 days prior to the first dose of study treatment and treatment-related toxicities have resolved to at least Grade 1;
Received any investigational drug (for any indication) within 5 half-lives of the drug or 14 days, whichever is longer;
Single group
RJK-RT2831 dose-escalation phase Ia
Drugthere are seven doses(1mg-160mg) in this part. The subjects will receive RJK-RT2831 injection twice a week by intravenous push or intravenous infusion for 4 weeks until the end of one dosing cycle (28 days). After one dosing cycle, if the subject tolerates, the subject will continue to receive treatment until the researcher believes that the subject no longer benefits, or the subject has disease progression, unacceptable toxicity, withdraws informed consent, dies, is lost to follow-up, or starts new anti-tumor treatment (whichever occurs first).
RJK-RT2831 Dose Expansion Phase Ib
Drugthere are four doses in this part. The subjects will be randomized in a 1:1 ratio to receive one dose level of RJK-RT2831 intravenous infusion twice a week for 4 weeks until the end of one dosing cycle (28 days).After one dosing cycle, if the subject tolerates, the subject will continue to receive treatment until the researcher believes that the subject no longer benefits, or the subject has disease progression, unacceptable toxicity, withdraws informed consent, dies, is lost to follow-up, or starts new anti-tumor treatment (whichever occurs first).
phase Ia and phase Ib: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
All AEs (except for CRS and TLS) will be graded according to NCI CTCAE V5.0, a common standard term for AE. CRS and TLS will be graded according to ASCTC Consensus (2019) and Cairo-Bishop grading system (Howard revised) respectively.
phase Ia: Maximum Tolerated Dose (MTD)
To assess the safety, tolerability, and maximum tolerated dose (MTD) of RJK-RT2831 in patients with hematologic malignancies.
phase Ia: Recommended Doses for Expansion (RDEs)
To determine the recommended doses for expansion (RDEs) in patients with hematologic malignancies.
phase Ib: Recommended Phase II Dose (RP2D)
To determine the recommended Phase II dose (RP2D) in patients with hematologic malignancies.
Cmax
Pharmacokinetic (PK) analysis of RT2831
Tmax
PK analysis of RT2831
Area under the concentration-time curve (AUC)
PK analysis of RT2831
Total Clearance (CL)
PK analysis of RT2831
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