Advanced Solid Tumor
Conditions
Brief summary
Phase 1/2 Study for IPG7236 Combined With Toripalimab in Participants With Advanced Solid Tumors
Detailed description
This is a phase 1/2, multicenter, non-randomized, open-label, dose-escalation and dose-expansion study. Part A (dose escalation) will adopt a standard "3+3" design with two cohorts (IPG7236 500 mg BID + Toripalimab 240 mg Q3W; IPG7236 800 mg BID + Toripalimab 240 mg Q3W) to determine the MTD and/or RP2D. Part B (dose expansion) will enroll approximately 40 CCR8-positive advanced solid tumor patients to further evaluate safety,tolerability and preliminary antitumor activity. The transition from Part A to Part B will be triggered after confirmation of RP2D based on safety, tolerability, PK and preliminary efficacy data.
Interventions
DRUGIPG7236
IPG7236: Part A: 500 mg BID or 800 mg BID, the dose in Part B is the RP2D confirmed in Part A, Oral (fasting: 1 hour before meal or 2 hours after meal, every 12±2 hours), Continuous daily administration, 21-day treatment cycle,Until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons for withdrawal
DRUGToripalimab Injection
Toripalimab Injection: 240 mg , Q3W, 21-day treatment cycle, the first infusion lasts at least 60 minutes; if well tolerated, subsequent infusions can be shortened to 30 minutes.
Sponsors
Nanjing Immunophage Biotech Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained before any study procedure is performed. 2. Men or women 18 years of age or older. 3. Histologically or cytologically confirmed advanced or recurrent malignant solid tumors that are metastatic or unresectable. (Subjects must submit tumor tissue sections from within the past 5 years for CCR8 expression testing. For subjects without paraffin-embedded tissues, a fine-needle aspiration biopsy may be performed. Subjects who cannot provide tumor tissue sections or undergo biopsy are only eligible for inclusion during the dose escalation phase. During the dose expansion phase, CCR8 positivity must be known or tumor tissue sections must be provided with confirmed CCR8 expression.) 4. Subjects must have failed or been intolerant to standard antitumor therapy, or lack a standard treatment regimen, or be deemed by the investigator as currently unsuitable for standard therapy. 5. According to the RECIST 1.1 criteria, there is at least one measurable lesion. 6. Life expectancy ≥ 3 months. 7. Subjects must be able to swallow the oral investigational drug. 8. The ECOG performance status score is 0 or 1. 9. Sufficient hematologic and organ function, with the following laboratory test values: 1. Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 75×10⁹/L; Hemoglobin ≥ 9 g/dL; lymphocytes ≥ 0.8×10⁹/L; 2. Renal: Creatinine clearance calculated by the Cockcroft-Gault method ≥ 50 mL/min or serum creatinine ≤ 1.5× upper limit of normal (ULN); 3. Hepatic: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3×ULN, or ≤ 5×ULN for subjects with liver metastases; total bilirubin ≤ 1.5×ULN, or ≤ 3×ULN for subjects with Gilbert syndrome or genetically equivalent conditions; 4. Coagulation: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5× upper limit of normal (ULN). 10. Patients must be willing and able to comply with all scheduled visits, treatments, laboratory tests, and other study requirements. 11. Male and female participants of reproductive potential who engage in heterosexual sexual behavior must agree to use reliable contraceptive methods (hormonal, barrier, or abstinence,etc.) for at least 4 months during the trial period and after the last study drug administration (refer to Appendix 13.1 of the protocol)
Exclusion criteria
1. Primary malignant tumors of the central nervous system or malignant tumors associated with human immunodeficiency virus (HIV) . 2. Previous use of CCR8-targeted therapy. 3. Received the following treatment within the specified time frame: 1. Planned major surgery within 4 weeks prior to the first dose administration (excluding minor procedures such as vascular access placement, gastrointestinal/biliary stent placement, or biopsy); 2. Immunotherapy or biological therapy administered within 28 days prior to the initial administration; 3. Chemotherapy \<21 days prior to the first dose, or mitomycin or nitrosoureas \< 42 days prior, or oral fluoropyrimidines \< 14 days prior; 4. Targeted small-molecule therapy or traditional Chinese medicine with antitumor indications administered within 14 days prior to the initial dose; 5. Hormone therapy or other adjuvant therapies are not permitted if initiated within 14 days prior to the first dose. Exceptions: anti-estrogen therapy, bisphosphonates, RANKL monoclonal antibodies, somatostatin analogs, and leuprorelin are permitted if initiated ≥ 14 days prior to the first dose. 6. Radiotherapy administered within 28 days prior to the first dose, or palliative radiotherapy within 14 days prior. Exception: Palliative radiotherapy (e.g., for analgesia) may be performed during the study drug administration period, provided that it is not permitted during the DLT observation period, any previously induced adverse events from radiotherapy have been resolved to grade \<2, and the radiotherapy was not directed at the target lesion. 7. Other investigational or treatments administered within 28 days prior to the first dose; 8. Any previous allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation; 4. Previous treatment-related toxicity has not yet resolved to a level of ≤ 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v6.0 or to the specified levels in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicity (DLT) | Up to 21 days after first dose (Cycle 1): To determine the DLT according to NCI CTCAE v6.0, and define the Maximum Tolerated Dose (MTD) and RP2D of IPG7236 in combination with toripalimab | Dose-Limiting Toxicity (DLT) is treatment-related adverse events (excluding disease progression/external causes) per NCI CTCAE v6.0, occurring within Cycle 1 Day 1-21,1) Unexplained death; 2) Hematological: Grade 4 neutropenia \>7d; Grade ≥3 febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 with clinical bleeding; Grade 4 anemia; 3) Non-hematological: Grade ≥3 (exceptions: Grade 3 nausea/vomiting/diarrhea \<3d with antiemetics; Grade 3 fatigue \<1w; pancreatitis-unrelated Grade ≥3 amylase/lipase; Grade ≥3 electrolyte disturbance resolving within 72h without complications; asymptomatic isolated lab abnormalities); Hepatotoxicity: Hy's Law (ALT/AST \>3×ULN + total bilirubin \>2×ULN + ALP \<2×ULN); AST/ALT \>8×ULN (or \>8×baseline for liver metastasis); AST/ALT \>5×ULN (or \>5×baseline for liver metastasis) ≥14d; Other Grade 4 non-hematological toxicity; 4) Toxicity requiring permanent study drug discontinuation or \<75% planned administration. Infusion-related reactions are not DLT; |
| Percentage of patients with adverse events | From first dose to 90 days after last dose or initiation of new anti-cancer therapy, whichever comes first | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) per iRECIST v1.1 | From first dose to disease progression or death (up to 24 months) | Objective Response Rate (ORR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) per iRECIST v1.1 criteria. |
| Disease Control Rate (DCR) per iRECIST v1.1 | From first dose to disease progression or death (up to 24 months) | Disease Control Rate (DCR) is defined as the percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) per iRECIST v1.1 criteria. |
| Duration of Response (DoR) per iRECIST v1.1 | From first documentation of objective response (CR or PR) to first documentation of progressive disease (PD) or death (up to 24 months) | Duration of Response (DoR) is defined as the time from first documentation of objective response (CR or PR) to first documentation of progressive disease (PD) or death due to any cause, per iRECIST v1.1 criteria. |
| Progression-Free Survival (PFS) per iRECIST v1.1 | From first dose to disease progression or death (up to 24 months) | Progression-Free Survival (PFS) is defined as the time from first dose to first documentation of progressive disease (PD) per iRECIST v1.1 criteria or death due to any cause, whichever occurs first. |
| Overall Survival (OS) per iRECIST v1.1 | From first dose to death due to any cause (up to 24 months) | Overall Survival (OS) is defined as the time from first dose to death due to any cause. |
| Peak Plasma Concentration (Cmax) of IPG7236 | From first dose to end of treatment, assessed up to 24 months | Peak plasma concentration of IPG7236, determined from plasma concentration-time profiles obtained at preset time points. |
| Trough Plasma Concentration (Cmin) of IPG7236 | From first dose to end of treatment, assessed up to 24 months | Trough plasma concentration of IPG7236, determined from plasma concentration-time profiles obtained at preset time points. |
| Area Under the Plasma Concentration-Time Curve (AUC) of IPG7236 | From first dose to end of treatment, assessed up to 24 months | Area under the plasma concentration-time curve of IPG7236, calculated using non-compartmental analysis from plasma samples collected at preset time points. |
| Time to Peak Plasma Concentration (Tmax) of IPG7236 | From first dose to end of treatment, assessed up to 24 months | Time to reach peak plasma concentration of IPG7236, determined from plasma concentration-time profiles obtained at preset time points. |
| Elimination Half-Life (T1/2) of IPG7236 | From first dose to end of treatment, assessed up to 24 months | Elimination half-life of IPG7236, calculated from the terminal phase of the plasma concentration-time curve obtained at preset time points. |
Countries
China
Contacts
CONTACTjian fei wang, CSO
Outcome results
None listed