A Phase I Study of JLM019 Injection (JLM019)

Inclusion Criteria:

1. Eighteen years of age or older;

2. 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.

3. 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;

4. 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.

5. 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;
6. For patients with accessible tumors, willingness to undergo on-study biopsy as scheduled in the protocol;
7. Eastern Cooperative Oncology Group (ECOG) performance status grade 0~1;
8. Life expectancy ≥ 3 months estimated by the Investigator;
9. 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);

10. 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).
11. 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.
12. Able to participate and willing to give written informed consent form.

Exclusion Criteria:

1. Allergy to JLM019 Injection components;
2. History of Grade 4 infusion-related, anaphylactic or allergic reaction to any previous monoclonal antibody or other Fc-based protein therapy;
3. Experienced any cardiovascular immune-related adverse event (irAE), or discontinued from that treatment due to a Grade 3 or higher irAE in previous ICI therapy;

4. Any serious or uncontrolled health conditions listed below:

   • Patients with concurrent infections requiring intravenous antimicrobial therapy within the past 2 weeks, or with unexplained fever (body temperature ≥ 37.5 °C);
   • History of vascular diseases within the past 6 months (including myocardial infarction, unstable angina, cerebrovascular diseases, and peripheral arterial or aortic diseases);
   • Uncontrolled hypertension (defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg on at least two separate occasions after antihypertensive treatment);
   • Individuals with active thrombosis, active bleeding, or pathological conditions associated with high bleeding risk (such as coagulation disorders);
   • Has an active autoimmune disease that has required systemic treatment (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment;

   • Any serious or uncontrolled cardiovascular condition, including but not necessarily limited to:

     1. Any history of myocarditis of any etiology;
     2. History of New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, cerebrovascular accident, cardiac hospitalization, or other acute uncontrolled heart disease within 6 months of scheduled C1D1;
     3. Left ventricular ejection fraction < 45 % on screening echocardiogram;
     4. Any clinically significant findings on screening EKG such as atrial or ventricular arrythmia (other than sinus tachycardia) or AV conduction abnormality such as left bundle branch block (such patients may be enrolled after cardiology clearance and Sponsor approval);
5. History of (non-infectious) pneumonitis / interstitial lung disease or current pneumonitis / interstitial lung disease;
6. Presence of any active central nervous system (CNS; brain or leptomeningeal) metastases. Solid tumor patients with CNS metastases are eligible if previously treated and there is no magnetic resonance imaging (MRI) evidence of progression for ≥ 8 weeks after treatment is complete and within 28 days prior to first dose of JLM019 Injection;
7. Prior organ allograft or allogeneic hematopoietic stem cell transplantation (HSCT). Lymphoma patients ≥ 3 months post-HSCT with no evidence of active graft versus host disease may be eligible upon approval by the Investigator or Sponsor;

8. Receipt of any of the following within the timeframes indicated, before first scheduled dose of JLM019 Injection:

   1. Checkpoint inhibitors, including PD-(L)1 (e.g., pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab), CTLA-4 (e.g., ipilimumab, tremelimumab) and Lag-3 (e.g., relatlimab), or costimulatory agonists (including but not limited to CD28, CD134 (OX40), CD137 (4-1BB)): 3 months (135 days for atezolizumab);
   2. Chemotherapy, small molecule anticancer agents (e.g., kinase inhibitors), or radiation: 2 weeks. Note: for lung cancers or mesotheliomas, radiation therapy to the lung that is > 30 Gy within 6 months;
   3. Other monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, antibody-like drugs, cytokines, cell therapies, or radio immunoconjugates: 4 weeks (2 weeks permissible with documented disease progression and approval by the medical monitor or Sponsor);
9. Currently participating in another clinical trial or has participated in another clinical trial within 4 weeks prior to the first dose of the investigational study treatment. Note: Patients who have entered the follow-up phase of another study may be enrolled if at least 4 weeks have elapsed since their last dose of study treatment;
10. Any condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days of the first dose of JLM019 Injection. Inhaled, intranasal or topical corticosteroids or adrenal replacement doses of corticosteroids are permitted in the absence of active autoimmune disease;
11. Received a live or live-attenuated vaccine within 30 days prior to the first dose of JLM019 Injection. Note: Administration of inactivated vaccines is allowed;
12. Received radiotherapy within 2 weeks of start of study treatment or had a history of radiation pneumonitis. Note: Patients must have recovered from all radiation-related toxicities, not required corticosteroids, and show no evidence of radiation pneumonitis. A 1-week washout period is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease;
13. Any second malignancy active within the previous 3 years( (except adequately treated carcinoma in situ of cervix, basal cell carcinoma or squamous cell skin carcinoma));
14. Patients with a history of AIDS, syphilis, or active hepatitis [For hepatitis B: positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV-DNA copy number above the upper limit of quantification; for hepatitis C: positive HCV antibody and HCV RNA copy number above the upper limit of quantification].
15. Pregnancy or lactation, and a woman of childbearing potential (WOCBP) who has a positive pregnancy test (within 7 days) prior to treatment;
16. Patients deemed unsuitable for participation in this study at the Investigator's discretion.