A Phase I Study of JLM019 Injection

1\. Dose Escalation Rules 1. If one Grade ≥ 2 treatment-emergent adverse event (TEAE) during the DLT observation period after the first dose at any dose level in Part A Dose Escalation will Add one more enrolled participant. If the supplementary enrolled subject also experiences ≥Grade 2 treatment-emergent adverse event will trigger the transition from accelerated titration to the traditional '3 + 3' cohort design. 2. At the '3 + 3' dose escalation stage, a sentinel cohort will be employed. If no DLTs occur in the sentinel cohort within 14 days after the drug administration, the other two patients will be enrolled at once in this dose group. If DLTs occur in the sentinel cohort, the other two patients will also be enrolled sequentially. 3. At the '3 + 3' dose escalation stage, 1. If the first 3 patients at this dose level experience no DLTs during the observation period, the dose will be escalated. 2. If 1 of the first 3 patients experienced DLTs or 2 of the first 3 patients of a cohort have Grade ≥ 2 CRS or neurotoxicity, another 3 patients will be enrolled in this group again, and dose escalation will be evaluated based on these 6 patients: 3. If 1 of 6 patients experience DLTs, the dose will be escalated. 4. If ≥ 2 of 6 patients experience DLTs, the dose escalation will be stopped. 5. If ≥ 2 of the first 3 patients experienced DLTs, the dose escalation will be stopped. 4. If MTD is reached at the starting dose level, a lower dose level will be considered. 5. Upon completion of DLT observation for each dose level, SRC will determine whether to terminate dose escalation or continue for further escalation or expand the dose groups based on a comprehensive review of the collected data. 6. The Recommended Expansion Dose (RED) will be determined based on the assessments of safety, efficacy, and PK data, regardless of whether the MTD is achieved. 2\. Statistical Analysis 2.1 Safety Analysis AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). AEs will be graded according to NCI CTCAE v6.0. AEs will be summarized by treatment group, System Organ Class (SOC), and Preferred Term (PT). Summaries will include (but not limited to): number of cases and incidence rates for all AEs, drug-related AEs, serious AEs (SAEs), drug-related SAEs, AEs leading to treatment discontinuation, and fatal AEs. For clinical safety assessments (laboratory tests, vital signs, physical examinations, 12-lead ECGs, etc.), treatment related changes from baseline will be described. Treatment-emergent abnormal findings will be listed in tables. During the dose-escalation phase, the incidence of DLTs will be calculated for each dose cohort. 2.2 PK Analysis Drug concentration data in peripheral blood will be analyzed by dose cohort according to scheduled PK sampling time-points. Individual and mean concentration-time profiles will be plotted for each dose cohort using both linear and semi-logarithmic scales. For summary statistics (e.g., mean concentration) and mean profile plots: Scheduled PK sampling time will be used. For individual patient concentration-time curves: Actual PK sampling time will be used. PK parameters including: Cmax, Tmax, t1/2, AUC0\~inf, AUC0\~t, CL/F, and Vz/F, will be analyzed by using non-compartmental analysis (NCA) for each dose cohort. Descriptive statistics will include number of subjects (n), arithmetic mean, standard deviation (SD), coefficient of variation (CV%), minimum, and maximum. For key parameters (e.g., Cmax and AUC0-inf), geometric mean and geometric CV% will also be reported. 2.3 PD Analysis Descriptive statistical methods will be used to analyze PD parameters by treatment groups. Time-course profiles of PD markers will be plotted. 2.4 ADA Analysis Descriptive summaries will be provided for the time and the proportion of ADA-positive subjects following investigational drug administration. ADA positive subjects will undergo Nab testing, and the time and incidence of Nab occurrence will be summarized. 2.5 Efficacy Analysis ORR and DCR will be reported as the number and percentage of subjects in each dose cohort, with 95 % confidence intervals (CIs) estimated by using the Clopper-Pearson method. For time-to-event endpoints (PFS, DOR, OS), median survival duration and corresponding 95 % CIs will be estimated for each dose cohort by using the Kaplan-Meier method. Kaplan-Meier survival curves will be plotted for the event occurrence over the time.