This is a Phase I, multicenter, single-arm, open-label clinical study designed to evaluate the safety and tolerability of JL19001 Injection as monotherapy (Phase Ia) or in combination with standard therapy (Phase Ib) in patients with AST and r/r B-NHL. Only the Phase Ia protocol design is registered at this time. A total of 6 dose cohorts are planned for Phase Ia, i.e., 1, 5, 10, 15, 20, and 25 μg/kg, with the administration route being subcutaneous injection. A traditional 3 + 3 dose escalation design will be used. The MTD and Recommended Maximum Add-on Dose (RMAD) for JL19001 Injection will be determined.

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for this study:

1. Age and Gender: Aged ≥ 18 years at the time of signing the Informed Consent Form (ICF), regardless of gender.

2. Disease Status: Patients with histologically or cytologically confirmed advanced solid tumors (AST) or relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) who have failed standard therapy, have no available standard treatment options, are intolerant to, or refuse standard therapy. This includes, but is not limited to, melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (SCCHN), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone B-cell lymphoma (MZL). Specific requirements for each tumor type are as follows:

   Melanoma: Advanced cutaneous or acral melanoma with progressive disease (PD) after ≥2 prior lines of systemic therapy. Prior treatment must include at least one immune checkpoint inhibitor (ICI; e.g., pembrolizumab, toripalimab, pucotenlimab, ipilimumab + nivolumab, atezolizumab) and at least one chemotherapy (e.g., dacarbazine, temozolomide, paclitaxel, nab-paclitaxel, cisplatin/carboplatin, fotemustine). For patients with BRAF V600, NRAS, or KITmutations, prior treatment must include at least one targeted therapy against the specific mutation and one ICI (as listed above). Patients unsuitable for or intolerant to the aforementioned treatments are excluded.

   RCC: Metastatic or unresectable clear cell RCC with PD after ≥1 prior line of therapy or intolerance to ≥1 prior line. Prior treatment must include at least one targeted therapy (e.g., sunitinib, pazopanib, sorafenib, axitinib, lenvatinib, anlotinib, vorolanib + everolimus) and one ICI (e.g., toripalimab, pembrolizumab, benmelstobart, nivolumab, ipilimumab).

   NSCLC: Stage IV NSCLC with PD after ≥2 prior lines of systemic therapy. For patients without driver alterations: Prior treatment must include at least one ICI (e.g., pembrolizumab, camrelizumab, tislelizumab, sintilimab, atezolizumab, sugemalimab, toripalimab, penpulimab, serplulimab, nivolumab + ipilimumab, ivonescimab) and/or platinum-based chemotherapy, plus one single-agent therapy (e.g., docetaxel, pemetrexed, gemcitabine, paclitaxel, vinorelbine, anlotinib).

   For patients with driver alterations (e.g., EGFRmutations, ALKfusions, ROS1fusions, BRAF V600mutations, NTRKfusions, METexon 14 skipping, RETalterations, KRAS G12Cmutations, or HER2mutations): Prior treatment must include at least one targeted therapy against the specific alteration and one platinum-doublet chemotherapy or single-agent therapy (as listed above). Patients unsuitable for or intolerant to the aforementioned treatments are excluded.

   SCCHN: Metastatic head and neck squamous cell carcinoma with PD after ≥2 prior lines of systemic therapy.

   Non-nasopharyngeal carcinoma: Prior treatment must include platinum-based chemotherapy and either an ICI (e.g., pembrolizumab, finotonlimab, toripalimab, nivolumab) or an EGFR monoclonal antibody (e.g., cetuximab).

   Nasopharyngeal carcinoma: Prior treatment must include platinum-based chemotherapy and an ICI (e.g., camrelizumab, toripalimab, tislelizumab, penpulimab, tagitanlimab). Patients unsuitable for or intolerant to the aforementioned treatments are excluded.

   r/r B-NHL: PD after ≥2 prior lines of systemic therapy. Prior treatment must include a regimen containing an approved CD20 antibody (e.g., rituximab, zuberitamab, ripertamab).

   Note: The later-line treatment status for all patients will be determined by the Investigator.

3. Measurable Disease: Presence of at least one evaluable tumor lesion according to RECIST 1.1 (solid tumors) or Lugano criteria (lymphoma). Note: Lesions previously irradiated are not considered target lesions unless there is documented progression within the irradiated field or persistence of the lesion >3 months after radiotherapy.

4. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (refer to Appendix 1: ECOG Performance Status).

5. Laboratory Parameters: Adequate organ function within 14 days prior to enrollment, defined as:

   Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L Platelet Count (PLT) ≥ 100 × 10⁹/L Hemoglobin (HGB) ≥ 90 g/L Total Bilirubin ≤ 1.5 × Upper Limit of Normal (ULN) Aspartate Aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases or hepatocellular carcinoma) Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases or hepatocellular carcinoma) Serum Creatinine ≤ 1.5 × ULN, or Calculated Creatinine Clearance ≥ 60 mL/min (Cockcroft-Gault formula) Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN International Normalized Ratio (INR) ≤ 1.5 × ULN

6. Life Expectancy: Expected survival ≥ 12 weeks.

7. Contraception and Pregnancy:

   Participants of childbearing potential and their partners must agree to use highly effective non-pharmacological contraceptive methods during the study and for at least 12 weeks after the last dose.

   Female participants of childbearing potential who are not surgically sterile must have a negative serum β-human chorionic gonadotropin (β-HCG) test within 7 days prior to the first dose and must not be breastfeeding.

8. Consent and Compliance: Ability to understand and voluntarily sign the ICF, and willingness to comply with scheduled visits as per protocol.

Exclusion Criteria:

Participants meeting any of the following criteria will be ineligible for this study:

1. Hypersensitivity: Known hypersensitivity to any component of the investigational product or to drugs of the same class.

2. CNS Metastases:

   Patients with active central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded.

   However, the following patients are allowed:

   ① Asymptomatic brain metastasis: No progressive CNS symptoms attributed to brain metastases, not requiring corticosteroids or requiring ≤ 10 mg/day prednisone (or equivalent), and lesion size ≤ 1.5 cm. These patients require regular brain imaging as a disease assessment site.

   ② Treated brain metastases: Stable brain metastases for at least 2 months (confirmed by two imaging assessments at least 4 weeks apart post-treatment), with no evidence of new or enlarging lesions, and discontinued steroids ≥ 3 days prior to the first dose. Stability must be established prior to the first dose.

3. Cardiac Conditions: Any of the following cardiac conditions:

   1. QTc interval > 450 ms (male) or > 470 ms (female).
   2. New York Heart Association (NYHA) Class III or IV congestive heart failure.
   3. Unstable angina, new-onset angina, or myocardial infarction within 6 months prior to screening.
   4. Clinically significant arrhythmias, including but not limited to complete left bundle branch block, second-degree atrioventricular block, or PR interval > 250 ms.
   5. Valvular heart disease ≥ Grade 2 (CTCAE).
   6. Left ventricular ejection fraction (LVEF) < 50% as measured by echocardiogram.
   7. Uncontrolled hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg); orthostatic hypotension or drug-induced hypotension (systolic BP < 90 mmHg or diastolic BP < 60 mmHg).
   8. Uncontrolled systemic disease despite regular treatment (e.g., diabetes).

4. Prior Immune Toxicity: History of prior immunotherapy with ≥ Grade 3 immune-related adverse events (irAEs) or ≥ Grade 2 immune-mediated myocarditis.

5. Coagulopathy: Hereditary bleeding diathesis or coagulopathy, or history of clinically significant bleeding disorders or arterial/venous thromboembolism (e.g., cerebrovascular events, deep vein thrombosis, pulmonary embolism) within 6 months prior to the first dose.

6. Autoimmune Disease: Active autoimmune diseases such as systemic lupus erythematosus, rheumatic diseases, Crohn's disease, ulcerative colitis, etc.

7. GI Perforation/Fistula: History of gastrointestinal perforation/fistula or risk factors for perforation within 6 months prior to the first dose.

8. GI Bleeding: Any ≥ Grade 3 gastrointestinal bleeding within 12 weeks prior to the first dose.

9. Transplantation: Prior allogeneic hematopoietic stem cell transplantation or organ transplantation.

10. Interstitial Lung Disease: History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or clinically significant active pneumonitis at screening (excluding radiation-induced fibrosis not requiring steroid treatment).

11. Effusions: Uncontrollable pleural effusion, pericardial effusion, or ascites, in the judgment of the Investigator.

12. Other Malignancies: History of any other active malignancy within 3 years prior to the first dose (except for curatively treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, or cancers with a disease-free survival > 1 year after radical treatment).

13. Surgery/Trauma: Major surgical procedure (excluding core needle biopsy) or significant traumatic injury within 4 weeks prior to the first dose, or planned elective surgery during the study period.

14. Prior Anticancer Therapy: Receipt of chemotherapy, radiotherapy, biologic therapy, endocrine therapy, targeted therapy, immunotherapy, or investigational agents within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose. Specific washout periods:Nitrosoureas or mitomycin C (within 6 weeks); oral fluoropyrimidines or small molecule targeted drugs (within 2 weeks); traditional Chinese medicine with anti-tumor indications (within 2 weeks).

15. Toxicity Recovery: Failure to recover from prior anticancer therapy toxicities to ≤ Grade 1 (per CTCAE v6.0), except for toxicities deemed safe by the Investigator (e.g., alopecia, Grade 2 peripheral neuropathy, hypothyroidism stable on hormone replacement).

16. IL-2/IL-15 Agonists: Receipt of IL-2 or IL-15 agonist therapy within 4 weeks prior to the first dose.

17. Immunomodulators: Receipt of immunomodulatory drugs (including but not limited to thymosin, interferon) within 2 weeks prior to the first dose.

18. Corticosteroids/Immunosuppressants: Receipt of systemic corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive therapies within 2 weeks prior to the first dose. Exceptions:Use of topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids; short-term prophylactic use (e.g., contrast allergy prevention).

19. Tuberculosis: Active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis > 1 year ago without adequate standard treatment.

20. Active Infection: Serious infection requiring intravenous antibiotics or hospitalization within 4 weeks prior to the first dose.

21. Viral Infections: Active viral infections, including:

    Active hepatitis B (HBsAg or HBcAb positive and HBV DNA > upper limit of normal).

    Active hepatitis C (HCV antibody positive and HCV RNA > upper limit of normal).

    Human Immunodeficiency Virus (HIV) infection. Syphilis infection. Note: Patients receiving prophylactic antiviral therapy (excluding interferon) are permitted.

22. Vaccinations: Receipt of live or attenuated live vaccines within 4 weeks prior to the first dose or anticipated receipt during the study period.

23. Other: Any other severe physical or psychiatric illness, laboratory abnormality, or other condition that, in the judgment of the Investigator, would increase the risk to the participant, interfere with study results, or make participation inappropriate.