A Phase I Study to Evaluate the Safety and Tolerability of JLM019 Injection in Patients With Advanced Malignancies
This is a multicenter, single-arm, open-label, dose escalation phase (Part A) and dose expansion (Part B) study to evaluate the safety and tolerability of JLM019 Injection in patients with advanced malignancies. The study subjects are adults with advanced malignancies including advanced solid tumors or relapsed/refractory lymphoma. During the dose escalation phase, the dose escalation scheme is the accelerated titration in 0.001 - 0.2 mg/kg cohorts plus a traditional '3 + 3' design in 0.6 - 10 mg/kg cohorts, jointly in nine dose cohorts 0.001, 0.01, 0.05, 0.2, 0.6, 1.5, 3, 6 and 10 mg/kg. JLM019 Injection is intended to be administered once a week (QW). However, the dose and interval of administration may be adjusted based on the acquired PK, PD, and safety data. Each treatment cycle is 28 days.The repeated dose is tentatively scheduled to be administered once weekly until one of the following occurs: disease progression, intolerable toxicity, requirement for new antitumor therapy, withdrawal of informed consent form, death, loss to follow-up, or other protocol-specified discontinuation conditions. Safety profile, DLT, MTD and RED of JLM019 Injection shall be assessed during and after treatment, with PK, PD, immunogenicity and Efficacy analyzed correspondingly.
• Eighteen years of age or older;
• Patients with histopathologically or cytologically confirmed advanced solid tumors (AST) or relapsed/refractory (r/r) Hodgkin's/Non-Hodgkin's lymphomas (HL/NHL, including transformed lymphomas):
‣ AST subtypes include but are not limited: colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), gastric cancer (GC), ovarian cancer (OV), renal cell carcinoma (RCC), melanoma, biliary tract cancer (BTC), alveolar soft part sarcoma (ASPS), etc.
⁃ HL/NHL subtypes include but are not limited: classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), mantle cell lymphoma (MCL), etc.
• Measurable disease as defined as:
‣ AST: At least one tumor lesion ≥ 10 mm in the longest diameter as assessed by computed tomography (CT);
⁃ HL/NHL: Fluorodeoxyglucose (FDG) avid disease by positron emission tomography (PET) and ≥ 1 lesion \> 15 mm in the longest diameter by \> 10 mm in the short axis, as assessed by CT;
• Patients with the following molecular profiles will be prioritized for enrollment:
‣ High tumor T-cell infiltration (e.g., elevated T-cell GEP score);
⁃ TMB \> 10 mut/Mb、MSI-H/dMMR status or POLE/POLD1 mutations. Absence of β2M and JAK1/JAK2 loss-of-function mutations.
• Submission of tumor biopsy representative of the current disease, which may consist of any of the following:
‣ Archived formalin-fixed paraffin-embedded (FFPE) tissue block;
⁃ At least 15-20 slides of tumor tissue from an FFPE block suitable for immunohistochemistry (IHC), including ≥ 10 % tumor content per section with ≥ 20 mm2 of evaluable tissue which may include ≤ 50 % tumor adjacent tissue;
⁃ A fresh tumor biopsy obtained by surgical excision or core needle procedure prior to the first dose of JLM019 Injection;
• For patients with accessible tumors, willingness to undergo on-study biopsy as scheduled in the protocol;
• Eastern Cooperative Oncology Group (ECOG) performance status grade 0\
• 1;
• Life expectancy ≥ 3 months estimated by the Investigator;
• Recovery to Grade ≤ 1 for any non-laboratory toxicity resulting from previous anticancer therapy prior to the first dose of investigational product (except alopecia, hearing loss, Grade ≤ 2 neuropathy, or endocrinopathy managed with replacement therapy);
⁃ Adequate baseline hematologic, renal, hepatic, and cardiac function as defined by:
∙ Lymphocyte ≥ 0.5 × 109/L；
‣ ANC ≥ 1.5 × 109/L;
‣ Platelet count (PLT) ≥ 100 × 109/L;
‣ Hemoglobin (HGB)≥ 90 g/L (no packed red blood cell transfusion within the prior 2 weeks);
‣ Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for patients with Gilbert's disease;
‣ Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2, as calculated by the Modification of Diet in Renal Disease (MDRD) formula;
‣ ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN if there is evidence of hepatic involvement by malignant disease);
‣ International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy in which PT or aPTT is within therapeutic range of intended use of anticoagulants;
‣ High sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro B-type natriuretic peptide (NT-proBNP) ≤ ULN (asymptomatic abnormalities may be permitted after clearance by cardiology consultation).
⁃ All patients and their partners must have no plans for conception from screening period and during the trial, and agree to practice effective contraception during the trial and for 4 months after the last dose of JLM019.
⁃ Able to participate and willing to give written informed consent form.