This trial is part of a multicenter, open-label Phase Ib/II clinical study evaluating the efficacy, safety, and tolerability of LM-108 in combination with anti-tumor therapy in patients with advanced solid tumors. Phase Ib of Cohort A1 determines the dose of LM-108 in combination with penpulimab + oxaliplatin + capecitabine. Phase II explores the efficacy and safety of LM-108 in combination with anti-tumor therapy in patients with advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
194
LM-108 injection is a monoclonal antibody that selectively clears regulatory T cells that infiltrate tumor sites. Penpulimab is a novel and differentiated programmed cell death protein 1 (PD-1) monoclonal antibody. Oxaliplatin is a third-generation platinum drug. Capecitabine is a fluoropyrimidine.
Tislelizumab is a humanized monoclonal antibody against Programmed cell death -Ligand-1(PD-1). Oxaliplatin is a third-generation platinum drug. Capecitabine is a fluoropyrimidine.
LM-108injection is a monoclonal antibody that selectively clears regulatory T cells that infiltrate tumor sites. Penpulimab is a novel and differentiated programmed cell death protein 1 (PD-1) monoclonal antibody.
LM-108 injection is a monoclonal antibody that selectively clears regulatory T cells that infiltrate tumor sites. Penpulimab is a novel and differentiated programmed cell death protein 1 (PD-1) monoclonal antibody.
Penpulimab is a novel and differentiated programmed cell death protein 1 (PD-1) monoclonal antibody. Oxaliplatin is a third-generation platinum drug. Capecitabine is a fluoropyrimidine.
Anhui Provincial Cancer Hospital
Hefei, Anhui, China
NOT_YET_RECRUITINGThe Second Hospital of Anhui Medical University
Hefei, Anhui, China
NOT_YET_RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGFujian Cancer Hospital
Fuzhou, Fujian, China
Incidence of dose limiting toxicity (DLT) events
Incidence of Phase Ib DLT events for Cohort A1.
Time frame: From first dose to 21days after first dose
Progression-free survival (PFS)
Defined as the time from first dose to first occurrence of disease progression or death due to any cause.
Time frame: The estimated time from randomization to patient disease progression was 10 months
Overall response rate (ORR)
After enrollment of all patients, the proportion of participants with the best overall efficacy rated as complete response or partial response according to criteria (RECIST1.1).
Time frame: The estimated duration was 16 months from enrollment of the first patient to 10 months after enrollment of the last patient
Duration of response (DOR)
Patient from the date of first documentation of objective remission of the tumor to the date of first documentation of objective progression of the tumor or the date of death due to any cause.
Time frame: The estimated duration was 16 months from enrollment of the first patient to 10 months after enrollment of the last patient
Disease control rate (DCR)
Proportion of participants with complete response, partial response, and stable disease as rated by RECIST v1.1 criteria for best overall efficacy after enrollment of all patients.
Time frame: The estimated duration was 16 months from enrollment of the first patient to 10 months after enrollment of the last patient
Overall survival (OS)
The time from randomization to death due to any cause.
Time frame: From randomization until patient death, it is expected to be evaluated up to 5 years
Number of patients with adverse events (AEs) and serious adverse events (SAEs)
Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: Baseline up to 90 days after the last dose
AE/SAE severity
Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Baseline up to 90 days after the last dose
Cmax
The highest blood concentration that occurs after administration. A1, A2: cycle1,0 hour, 0 after LM-108, 4.5hours after penpulimab, 0 in 2, 4 and 6 cycles; 0 of cycle9 and every 4 cycles. A3, A4: 0hour, instantly after LM-108, and after penpulimab, 1, 4, 24, 48, 168hours, and 336hours after penpulimab, 0 in 2, 4 and 6 cycles. Each cycle is 21 days.
Time frame: A1/A2: 0hour in cycle 1, end of LM-108, 4.5hours post penpulimab; 0hour of 2,4,6cycles; 0hour of cycle 9 and every 4cycles. A3/A4: 0hour in cycle 1, end of LM-108, end of penpulimab, 1, 4, 24, 48, 168, 336hour; 0hour of 2, 4, 6cycles. 21 days as a cycle
Tmax
The time it takes to reach the peak concentration after dosing.
Time frame: A1/A2: 0hour in cycle 1, end of LM-108, 4.5hours post penpulimab; 0hour of 2,4,6cycles; 0hour of cycle 9 and every 4cycles. A3/A4: 0hour in cycle 1, end of LM-108, end of penpulimab, 1, 4, 24, 48, 168, 336hour; 0hour of 2, 4, 6cycles. 21 days as a cycle
T1/2
The time it takes for the concentration of the drug to drop by half.
Time frame: A1/A2: 0hour in cycle 1, end of LM-108, 4.5hours post penpulimab; 0hour of 2,4,6cycles; 0hour of cycle 9 and every 4cycles. A3/A4: 0hour in cycle 1, end of LM-108, end of penpulimab, 1, 4, 24, 48, 168, 336hour; 0hour of 2, 4, 6cycles. 21 days as a cycle
Clearance rate (CL)
The number of apparent volumes of distribution of the drug cleared from the body per unit of time.
Time frame: A1/A2: 0hour in cycle 1, end of LM-108, 4.5hours post penpulimab; 0hour of 2,4,6cycles; 0hour of cycle 9 and every 4cycles. A3/A4: 0hour in cycle 1, end of LM-108, end of penpulimab, 1, 4, 24, 48, 168, 336hour; 0hour of 2, 4, 6cycles. 21 days as a cycle
Apparent volume of distribution (Vz)
The ratio constant of the amount of drug in the body to the concentration of the drug in the blood when the drug reaches homeostasis in the body. A1/A2: 0hour in cycle 1, end of LM-108, 4.5hours post penpulimab; 0hour of 2,4,6cycles; 0hour of cycle 9 and every 4cycles. A3/A4: 0hour in cycle 1, end of LM-108, end of penpulimab, 1, 4, 24, 48, 168, 336hour; 0hour of 2, 4, 6cycles. 21 days as a cycle
Time frame: A1/A2: 0hour in cycle 1, end of LM-108, 4.5hours post penpulimab; 0hour of 2,4,6cycles; 0hour of cycle 9 and every 4cycles. A3/A4: 0hour in cycle 1, end of LM-108, end of penpulimab, 1, 4, 24, 48, 168, 336hour; 0hour of 2, 4, 6cycles. 21 days as a cycle
Incidence of Immunogenicity indicators: anti-drug antibodies (ADA)
Usually refers specifically to antidrug-binding antibodies.
Time frame: 0h on Day 1 of Cycles 1, 2, 4, and 6, 0 hours on Day 1 of Cycle 9 and every 4 cycles thereafter, end of treatment/early withdrawal follow-up, and Safety Follow-up Visit 1 (30 days after last dose). Each cycle is 21 days
Incidence of Immunogenicity indicators: neutralizing antibodies (Nab)
Refers to anti-drug antibodies that interfere with the interaction of a drug with its target.
Time frame: 0h on Day 1 of Cycles 1, 2, 4, and 6, 0 hours on Day 1 of Cycle 9 and every 4 cycles thereafter, end of treatment/early withdrawal follow-up, and Safety Follow-up Visit 1 (30 days after last dose). Each cycle is 21 days
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The First Hospital of Lanzhou University
Lanzhou, Gansu, China
NOT_YET_RECRUITINGGansu Wuwei Tumour Hospital
Wuwei, Gansu, China
NOT_YET_RECRUITINGPeking University Shenzhen Hospita
Shenzhen, Guangdong, China
NOT_YET_RECRUITINGGuangxi Medical University Cancer Hospital
Nanning, Guangxi, China
NOT_YET_RECRUITINGTangshan People's Hospital
Tangshan, Hebei, China
NOT_YET_RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
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