A Phase I Study of JL19001 Injection Alone or in Combination With Standard Therapy in Patients With Advanced Solid Tumors or Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
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.
⁃ Participants must meet all of the following criteria to be eligible for this study:
• Age and Gender: Aged ≥ 18 years at the time of signing the Informed Consent Form (ICF), regardless of gender.
• 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.
• 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.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (refer to Appendix 1: ECOG Performance Status).
• 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
• Life Expectancy: Expected survival ≥ 12 weeks.
• 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.
• Consent and Compliance: Ability to understand and voluntarily sign the ICF, and willingness to comply with scheduled visits as per protocol.