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

NCT06468358 | Recruiting Phase 1

• 1 other identifier: TRIGGERCD8
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (10)

• Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0)

  Incidence of treatment-emergent adverse events (TEAEs) and treatment-related adverse events reported per NCI-CTCAE v5.0

  up to 60 days following last dose

• Incidence and severity of serious adverse events (SAEs) and other special interest (immune-related AEs)

  According to NCI-CTCAE v5.0

  up to 60 days following last dose

• Incidence of Dose limiting toxicity (DLT)

  The DLT for this study is defined per CTCAE 5.0 and will be evaluated in the Cycle 1 of treatment in the dose escalation part. If dosing delay occurs, the DLT evaluation should be correspondingly extended to 14 days after the second dosing.

  At the end of Cycle 1 (each cycle is 28 days)

• Maximum tolerance toxicity (MTD) and recommended dose for Phase II (RP2D) definition

  MTD and RP2D based on the safety data collected during the dose escalation phase (Phase I)

  up to 1 year

• Overall response rate (ORR)

  Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria over the total number of evaluable patients

  From first participant until last participant assessment, an average of 8 months

• Disease control rate (DCR)

  Percentage of patients whose best overall response is either a Complete Response, a Partial Response or Stable Disease according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria over the total number of evaluable patients.

  From first participant until last participant assessment, an average of 8 months

• Duration of overall Response (DoR) by RECIST version 1.1

  Time from the date of first documented response (CR or PR) to the date of first documented disease progression according to RECIST 1.1 criteria or the date of death due to underlying cancer.

  From first participant until last participant assessment, an average of 8 months

• Progression Free Survival (PFS) by RECIST version 1.1

  Time from the first infusion of LB1410 and LB4330 to the date of first documented tumor progression according to RECIST 1.1 criteria or death due to any cause, whichever occurs first over evaluable patients.

  From first participant until last participant assessment, an average of 8 months

• DDC

  Time from the date of first documented CR, PR or SD to the date of first documented disease progression according to RECIST 1.1 criteria or the date of death due to any cause.

  From first participant until last participant assessment, an average of 8 months

• Overall Survival (OS) duration

  Time from first LB1410 and LB4330 infusion to the date of death due to any cause over evaluable patients.

  From first participant until last participant assessment, an average of 1 year

Secondary Outcomes (5)

• Pharmacokinetics of LB1410 and LB4330: Maximum plasma concentration of the study drug (Cmax)

  Through study completion, an average of 1 year

• Pharmacokinetics of LB1410 and LB4330: Area Under the concentration-time curve (AUC)

  Through study completion, an average of 1 year

• Pharmacokinetics of LB1410 and LB4330: Clearance

  Through study completion, an average of 1 year

• Pharmacokinetics of LB1410 and LB4330: Terminal elimination half-life ( T½)

  Through study completion, an average of 1 year

• Evaluation of immunogenicity of each antibody drug in the combinations

  Up to 60 days following last dose

Study Arms (2)

Phase Ib, Dose Escalation of LB1410 in combination with LB4330

EXPERIMENTAL

Up to 4 dose cohorts will be enrolled in the dose-escalation part with the standard 3+3 dose escalation algorithm approach.

Drug: LB1410; Drug: LB4330

Phase II, Expansion Cohorts of LB1410 in combination with LB4330

EXPERIMENTAL

This part includes IIa and IIb. Phase IIa will be enrolled subjects at the dose level with initial anti-tumor activity observed in Phase Ib, the numbers of patients enrolled in the phase IIa could be adjusted based on previously available safety and preliminary efficacy data; the dose level of the phase IIb is the RP2D dose level determined in the phase Ib. The planned expanded cohorts are as follows: Cohort A: pancreatic ductal adenocarcinoma; Cohort B: cholangiocarcinoma; Cohort C: colorectal cancer; Cohort D: recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; Cohort E: other solid tumors (non-small cell lung cancer, gastric or gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, hepatocellular carcinoma, renal cell carcinoma, cervical squamous cell carcinoma, and endometrial carcinoma).

Drug: LB1410; Drug: LB4330

Interventions

LB1410 DRUG

anti-PD-1/TIM3 bispecific antibody

Phase II, Expansion Cohorts of LB1410 in combination with LB4330; Phase Ib, Dose Escalation of LB1410 in combination with LB4330

LB4330 DRUG

anti-claudin18.2/IL-10 fusion protein

Phase II, Expansion Cohorts of LB1410 in combination with LB4330; Phase Ib, Dose Escalation of LB1410 in combination with LB4330

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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).

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.

Sponsors & Collaborators

• L & L Bio Co., Ltd., Ningbo, China: lead
• Shanghai East Hospital: collaborator

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 201114, China

RECRUITING

Study Officials

• Caicun Zhou

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Luan

CONTACT

+86-21-54152522; luanyn2@lnlbio.com

Caicun Zhou

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase Ib/II, open, dose-escalation and expansion study of LB1410 in combination with LB4330 in patients with advanced or metastatic solid tumors. The study includes 2 parts, Part 1 Dose Escalation and Part 2 Dose Expansion. Initially, participants with pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, ovarian, fallopian tube, or primary peritoneal cancer, non-small cell lung cancer, gastric and gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, hepatocellular carcinoma, renal cell carcinoma, cervical squamous cell carcinoma, and endometrial carcinoma will be enrolled in the study; additional tumor types may be explored and added in a future amendment to the CSP.

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 21, 2024
• Study Start: June 19, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

CN (1)