Advanced Solid Tumor
Conditions
Brief summary
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.
Interventions
DRUGLM-108 injection+Penpulimab+ Oxaliplatin+Capecitabine
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.
DRUGLM-108 injection 10mg/kg +penpulimab
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.
DRUGLM-108 injection 600mg + penpulimab
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.
DRUGenpulimab+ Oxaliplatin+Capecitabine
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.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be at least 18 years old. 2. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1. 3. At least 1 measurable lesion as determined by RECIST v1.1 assessment. Positron emission tomography (PET) scans and ultrasonography cannot be used for diagnostic purposes. 4. All acute toxicities due to prior antineoplastic therapy or surgery have resolved to Grade 0-1 (according to NCI-CTCAE v5.0) or to the level specified by the enrollment/
Exclusion criteria
. Other toxicities that, in the opinion of the investigator, do not pose a safety risk to the participant, such as alopecia, fatigue, and hearing loss, are excluded. 5. Have adequate organ and bone marrow function, defined below: 1. Routine blood tests: (no transfusion, no granulocyte colony-stimulating factor (G-CSF), no drug correction) white blood cell count (WBC) ≥ 3,000/mm3 (3.0 × 109/L), neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 109/L), platelet count (PLT) ≥ 100,000/mm3 (100 × 109/L), hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L); 2. Biochemical tests: serum albumin ≥ 3.0 g/dL (30 g/L), serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (calculated using the Cockcroft-Gault formula), total bilirubin (BIL) ≤ 1.5 times the upper limit of normal (ULN); Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) levels ≤ 2.5 times the upper limit of normal (ULN), and patients with liver metastases should ≤ 5× ULN; 3. The international normalized ratio (INR) is ≤ 1.5, and the prothrombin time (PT) and activated partial thromboplastin time (APTT) are ≤ 1.5 times ULN; 4. Urine protein\< 2+; If the urine protein ≥ 2+, the 24-hour urine protein quantification shows that the protein must be ≤ 1 g; 5. Cardiac function: left ventricular ejection fraction ≥ 50% on echocardiography. 6. Expected survival ≥ 12 weeks; 7. Non-childbearing is defined as a woman who has reached a postmenopausal state, or who has had a medically documented bilateral oophorectomy. Male participants and female participants of childbearing potential must agree to use 1 medically approved form of contraception for the duration of the trial and for 6 months after the last dose of the trial drug or 9 months after the last dose of the chemotherapy drug (oxaliplatin), whichever is later, and a negative serum pregnancy test within 3 days prior to starting the study drug and not lactating. 8. With the consent of the person and has signed the informed consent form, willing and able to comply with the planned visits, study treatment, laboratory tests, and other trial procedures. Enrollment criteria applicable to each cohort: Cohorts A1 and A2 must meet the following enrollment criteria: 9. Patients with a pathologically confirmed diagnosis of Gastric cancer (GC) or Gastroesophageal junction cancer (GEJC), evidence of unresectable advanced or metastatic disease, and histologic confirmation of adenocarcinoma. 10. Provide negative reports of human epidermal growth factor receptor 2 (HER2) overexpression or amplification; HER2 overexpression or amplification negative is defined as Immunohistochemistry (IHC) 0/1+, or IHC 2+ with Fluorescence In Situ Hybridization (FISH)/In Situ Hybridization (ISH) negative. 11. No prior systemic therapy (including anti-HER-2 therapy) for advanced or metastatic GC/GEJC. Patients who have received prior adjuvant or neoadjuvant therapy for GC/GEJC (including: chemotherapy, radiotherapy, or chemoradiotherapy) have a time of first recurrence or disease progression greater than 6 months from the end of the last treatment. Participants who have previously received anti-tumor traditional Chinese medicine preparations are allowed, but must be discontinued at least 14 days prior to enrollment. 12. Participants should provide tumor tissue samples: fresh specimens (preferred) or formalin-fixed, paraffin-embedded tumor tissue, or microneedle aspiration tissue collected at radiotherapy-naïve sites within approximately 24 months prior to enrollment (specimens within 6 months prior to the first dose of study drug are recommended and no systemic therapy has been received since the sample was obtained). For participants who are unable to provide tissue samples but meet other enrollment conditions, the investigator and the sponsor will jointly decide whether to enroll. Cohorts A3 and A4 need to meet the following enrollment criteria: 13. Patients with pathologically confirmed solid tumors with evidence of advanced or metastatic unresectable disease. 14. Patients with advanced or metastatic solid tumors who have failed at least one prior line of standard therapy. Participants who have previously received anti-tumor traditional Chinese medicine preparations are allowed, but must be discontinued at least 14 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicity (DLT) events | From first dose to 21days after first dose | Incidence of Phase Ib DLT events for Cohort A1. |
| Progression-free survival (PFS) | The estimated time from randomization to patient disease progression was 10 months | Defined as the time from first dose to first occurrence of disease progression or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | The estimated duration was 16 months from enrollment of the first patient to 10 months after enrollment of the last patient | 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. |
| Overall survival (OS) | From randomization until patient death, it is expected to be evaluated up to 5 years | The time from randomization to death due to any cause. |
| Number of patients with adverse events (AEs) and serious adverse events (SAEs) | Baseline up to 90 days after the last dose | Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| AE/SAE severity | Baseline up to 90 days after the last dose | Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
| Cmax | 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 | 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. |
| Overall response rate (ORR) | The estimated duration was 16 months from enrollment of the first patient to 10 months after enrollment of the last patient | 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). |
| T1/2 | 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 | The time it takes for the concentration of the drug to drop by half. |
| Clearance rate (CL) | 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 | The number of apparent volumes of distribution of the drug cleared from the body per unit of time. |
| Apparent volume of distribution (Vz) | 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 | 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 |
| Incidence of Immunogenicity indicators: anti-drug antibodies (ADA) | 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 | Usually refers specifically to antidrug-binding antibodies. |
| Incidence of Immunogenicity indicators: neutralizing antibodies (Nab) | 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 | Refers to anti-drug antibodies that interfere with the interaction of a drug with its target. |
| Tmax | 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 | The time it takes to reach the peak concentration after dosing. |
| Duration of response (DOR) | The estimated duration was 16 months from enrollment of the first patient to 10 months after enrollment of the last patient | 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. |
Countries
China
Contacts
Primary ContactLin Shen, Doctor
Outcome results
None listed