A Study to Evaluate LB1410 in Combination With LB4330 in Patients With Advanced or Metastatic Solid Tumors

Recruiting now · Phase 1/Phase 2

Conditions studied: Solid Tumor

In brief

This is a phase Ib/II, open, dose-escalation and expansion study of an anti-PD1/TIM3 bispecific antibody，LB1410 in combination with an anti-Claudin18.2/IL-10 fusion protein, LB4330 in patients with advanced or metastatic solid tumors.

Key facts

Study ID

NCT06468358

Run by

L & L Bio Co., Ltd., Ningbo, China

People needed

194

Starts

2024-06-19

Expected to finish

2027-12-30

Last updated by the study team

2025-09-11

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Must be ≥ 18 years of age when signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 without deterioration in the past 2 weeks.
• Estimated life expectancy of ≥12 weeks.
• Baseline IL-6 levels below 40 pg/mL.
• Histologically or cytologically documented advanced and metastatic solid tumors for which can't tolerate standard treatment, standard treatment fails, or no standard treatment is available at this stage.
• Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at screening.
• Adequate hematologic function prior to registration for protocol therapy defined as the following criteria:
• absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, without the use of granulocyte colony-stimulating factor such as filgrastim in the 2 weeks prior to study treatment (≤ 14 days);
• platelet count ≥ 120 × 10\^9/L, without transfusion or use of drugs like recombinant human platelet growth factor in the 2 weeks prior to study treatment (≤ 14 days), for HCC patients, platelet count ≥ 100 × 10\^9/L;
• hemoglobin ≥ 90 g/L, without transfusion or use of drugs like erythropoietin in the 2 weeks prior to study treatment (≤ 14 days).
• Both AST and ALT ≤ 3 × ULN (both AST and ALT < 5 × ULN for subjects with known hepatocellular carcinoma or hepatic metastases); total bilirubin ≤ 1.5 × ULN (except for subjects with elevated serum bilirubin due to documented underlying conditions such as Gilbert's syndrome or familial benign unconjugated hyperbilirubinemia); for bile duct cancer patients, total bilirubin ≤ 2 × ULN; and serum albumin ≥ 30 g/L.
• Adequate renal function defined as: serum creatinine ≤ 1.5 × ULN, and creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula).
• Requirements for coagulation function are as follows:
• activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;
• international normalized ratio (INR) ≤ 1.5 × ULN (INR ≤ 3 × ULN for subjects receiving warfarin anticoagulant therapy).
• Any prior anti-tumor therapies (including endocrine/chemotherapy/targeted therapy/immunotherapy) before treatment should washout:
• at least 4 weeks for biological therapy (e.g., antibodies);
• at least 2 weeks or 5 half-lives (whichever is longer) for small molecule drugs, including 5-FU or its derivatives; at least 6 weeks for nitrosoureas and mitomycin;
• at least 2 weeks for Chinese herbal medicine used for indications of anti-tumor activity;
• at least 4 weeks for any systemic therapeutic investigational drugs;
• at least 2 weeks for any radiotherapy;
• any related toxicities or prior adverse events resolved to baseline or ≤ NCI CTCAE 5.0 grade 1 (excluding toxicities without safety risk judged by the investigator, such as alopecia, grade 2 peripheral neuropathy, stable hypothyroidism under hormone replacement therapy, etc.).
• Phase Ib dose escalation additional inclusion criteria: histologically or cytologically documented advanced malignant solid tumors (preferably pancreatic ductal adenocarcinoma, cholangiocarcinoma, ovarian cancer, microsatellite stable colorectal cancer, advanced solid tumors previously treated with anti-PD-1/PD-L1 inhibitors, such as gastric or gastroesophageal junction adenocarcinoma, or other solid tumors determined by the investigator and sponsor);
• Phase II (phase IIa and IIb) dose expansion cohort A additional inclusion criteria:
• must have received at least one but no more than two prior lines of systemic therapy;

You may not qualify if…

• Pregnancy, lactation, or breastfeeding.
• Any prior ≥ Grade 3 immune-related adverse events (irAEs) while receiving immunotherapy or any grade irAE leading to discontinuation in prior immunotherapy; or grade 4 myelosuppression during prior antitumor therapy.
• Known history of allergy or severe hypersensitivity reactions to other monoclonal antibodies or intravenous immunoglobulins such as anti-PD1/anti-PD-L1 antibodies, TIM-3, interleukin-10, or any of its excipients.
• Active autoimmune disease or symptomatic history of autoimmune disease (including celiac disease) requiring pharmacological doses of systemic corticosteroids and/or immunosuppressive. Exceptions include vitiligo, relieved asthma/atopic disease, type 1 diabetes or hypothyroidism treatable with alternative therapy and achieving clinical stability during screening, or any other autoimmune disease after discussion with the principal investigator and sponsor.
• Requirement for systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days prior to the planned first dose of study intervention. Inhalational or topical corticosteroids and adrenal replacement steroids (≤ 15 mg prednisone once daily equivalent) are allowed in the non-active autoimmune disease. Ophthalmic, nasal, inhaled, and intra-articular corticosteroids are allowed; short-term use of glucocorticoids for prophylactic treatment (e.g., prevention of contrast media allergy) is allowed.
• Any of the following prior treatments:
• major surgical procedure (e.g., laparotomy, thoracotomy, organ resection, etc.), severe trauma, etc. (Replacement of intravenous drip droppers is acceptable) within 4 weeks prior to first dose, or not recovered from prior surgery; surgery within 14 days prior to the first dose to improves tumor complications or reduces tumor risk (e.g., cervical cancer subjects undergoing nephrostomy or urethral stent placement); significant surgery planned within 30 days after the first dose (except for local surgeries such as placement of systemic ports, core needle biopsy, and prostate biopsy, provided the surgery is completed at least 24 hours before the first dose of study intervention);
• receipt of live vaccine or live attenuated vaccine within 4 weeks prior to first dose of study intervention;
• use of modulating drugs within 14 days prior to first dose of study intervention, including but not limited to thymosin peptide, interleukin-2, interferon, etc.;
• history of allogeneic organ transplant, allogeneic hematopoietic stem cell transplant, or bone marrow transplant.
• Prior use of drugs with the same mechanism of action as the study drug (e.g., anti-PD1 antibody in combination with anti-TIM3 antibody, PD1/TIM3 bispecific antibody, or IL-10-containing drug).
• Active infection including syphilis, hepatitis B (HBsAg positive and HBV-DNA > 200 IU/mL or 1000 cps/mL or HBV DNA above the lower limit of detection if the lower limit of the study center is above 200 IU/mL), hepatitis C (Patients with HCV antibody positive but HCV-RNA < lower limit of the study center were admitted).
• History of other malignant tumors within the past 3 years.
• Subjects with meningeal metastasis, spinal cord compression, or symptomatic unstable brain metastases or requiring steroids and/or antiepileptic drugs within 4 weeks before enrollment.
• Severe infection requiring systemic antibiotic therapy within 14 days prior to first dose, or active infection requiring systemic treatment.
• Uncontrolled or poorly controlled diabetes (glycated hemoglobin ≥ 7.5 at screening), asthma, chronic obstructive pulmonary disease, or other diseases that pose a risk to study participants.
• Any syncope or seizure within 28 days prior to first dose of the study intervention.
• Known gastric bleeding lesions or patients considered to be at high risk of gastric bleeding by the investigator.
• Known presence of diseases such as symptomatic irritable bowel syndrome (such as chronic nausea, persistent recurrent vomiting or diarrhea) and gastric bleeding or intestinal obstruction.
• Known history of serious cardiovascular and cerebrovascular diseases, including but not limited to:
• uncontrolled cardiovascular diseases within 3 months before the study, including but not limited to congestive heart failure required treatment (NYHA > II), uncontrolled hypertension (resting blood pressure ≥ 160/100 mmHg), uncontrolled arrhythmia;
• myocardial infarction, unstable angina, viral myocarditis, pericarditis, cerebrovascular accident, or other acute uncontrolled heart disease within the recent 6 months;
• Electrocardiogram: Female QTcF > 470 milliseconds (ms), Male QTcF > 450 ms (QTcF = QT/RR1/3), or congenital long QT syndrome;
• Echocardiographic assessment: Left ventricular ejection fraction (LVEF) ≤ 50% measured by multiple-gated acquisition (MUGA) or echocardiography.
• Known evidence of interstitial lung disease, symptomatic or may interfere with suspicious findings or management of drug-related pulmonary toxicity.

Where it is running

• Shanghai East Hospital — Shanghai, Shanghai Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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