Gastric Cancer, Pancreatic Adenocarcinoma, Solid Tumor
Conditions
Keywords
advanced solid tumors, Gastric Cancer, Esophagogastric Junction Cancer, Pancreatic Adenocarcinoma, Claudin 18.2, CLDN18.2, monoclonal antibody
Brief summary
This is an open, two-stage, phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of AB011 injection in patients with CLDN18.2-positive advanced solid tumors.
Detailed description
This study is an open, two-stage, phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of AB011 injection in patients with CLDN18.2-positive advanced solid tumors. The study is composed of two stages: stage I is single treatment and stage II is combo treatment.
Interventions
DRUGAB011 Injection
Stage 1 Single treatment: AB011 Injection with dose escalation of 1mg/kg up to 40mg/kg, as well as dose expansion with recommended dose level from dose escalation. Stage 2 Combo Treatment: AB011 combine XELOX( GC) or Gem/nab-P (PC) Injection with dose escalation of 10mg/kg up to 30mg/kg, as well as dose expansion with recommended dose level from dose escalation.
Sponsors
Shanghai East Hospital
CARsgen Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Stage 1: Inclusion Criteria: * 1\. Aged 18 to 80 years, either sex; * 2\. Patients with histologically or cytologic confirmed advanced solid tumors should have failed the standard treatment, or have no standard treatment regimen available, or have no access to standard treatment; * 3\. Tumor tissue samples is CLDN18.2 positive; * 4\. According to RECIST1.1, there are at least one evaluable tumor lesion during dose escalation period (stage 1), and at least one measurable tumor lesion during dose expansion period (stage 2); * 5\. The ECOG score is 0 to 1; * 6\. Expected survival \> 3 months; * 7\. Various organs in good condition; * 8\. Fertile eligible patients (male and female) and their partners are willing to use a reliable method of contraception (hormones, barriers or abstinence) during the study and within 90 days after the last study treatment; women of childbearing potential must be tested for serum or urine pregnancy within 7 days before enrollment with negative results; * 9\. Patients are informed of this study before the trial and sign written informed consent form.
Exclusion criteria
* 1\. Received anti-tumor therapies within 4 weeks prior to first administration of study drug, except: within 6 weeks for nitrosoureas or mitomycin C, within 2 weeks or 5 half-life of drugs (whichever longer) for oral fluorouracils and small molecular targeted drugs, and within 2 weeks for traditional Chinese medicines with indications of anti-tumor; * 2\. Received other non-marketed clinical trial drugs within 4 weeks prior to first administration of study drugs; * 3\. Received major surgery or had significant trauma within 4 weeks prior to first administration of study drug; * 4\. Received systemic corticosteroids or other immunosuppressors within 14 days prior to first administration of study drug; * 5\. Patients with AEs from previous treatment that have not recovered to ≤1 (CTCAE 5.0 ); * 6\. Patients have central nervous system (CNS) metastasis or meningeal metastasis, or other evidences which demonstrate the CNS metastasis or meningeal metastasis are not controlled, resulting that patients are not eligible for enrollment at the investigator's discretion; * 7\. Patients with any active infection which requires systemic treatment with of anti-infection currently; * 8\. Patients with medical history of immune deficiency; * 9\. Patients with hepatitis B; * 10.Patients with HCV infection but who with the HCV-RNA lower than the lower limit of detection can be enrolled ; * 11.Patients with interstitial lung disease or Pulmonary function abnormalities which were identified by the investigator as clinically significant; * 12.Patients who received any anti-CLDN18.2 treatment; * 13.Patients with significant medical history of cardiovascular and cerebrovascular diseases; * 14.Patient with high risks of gastrointestinal hemorrhage at the investigator's discretion; * 15.Patients who need long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) ; * 16.Known alcohol use or drug dependence; * 17.Patients with mental disorders or poor compliance; * 18.Pregnant or lactating women; * 19.Past severe allergic reactions or allergies to known components of AB011 injection ; * 20.Persistent recurrent vomiting (defined as ≥3 vomiting in 24 hours); * 21\. Have other uncured malignant tumors in the past 5 years or at the same time, except cervical carcinoma in situ, basal cell carcinoma of the skin and other tumors with very low malignant degree; * 22.Live attenuated vaccine was administered within 4 weeks prior to initial administration of the study drug; * 23.Patients who with other serious systemic diseases or cannot participate in this trial due to other reasons, at the investigator's discretion. Stage 2: Inclusion Criteria: * 1\. Aged 18 to 80 years, either sex; * 2\. Patients with histologically or cytologic confirmed advanced gastric/oesophagus- gastric junction cancer or pancreatic cancer without systemic therapy (neoadjuvant therapy or postoperative adjuvant therapy, no tumor progression or recurrence within 6 months of last medication) * 3\. Tumor tissue samples is CLDN18.2 positive ; * 4\. According to RECIST1.1, there are at least one evaluable tumor lesion during dose escalation period (stage 1), and at least one measurable tumor lesion during dose expansion period (stage 2); * 5\. The ECOG score is 0 to 1; * 6\. Expected survival \> 3 months; * 7\. Various organs in good condition; * 8\. Fertile eligible patients (male and female) and their partners are willing to use a reliable method of contraception (hormones, barriers or abstinence) during the study and within 90 days after the last study treatment; women of childbearing potential must be tested for serum or urine pregnancy within 7 days before enrollment with negative results; * 9\. Patients are informed of this study before the trial and sign written informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage1：Incidence of adverse events AE of single and multiple dose (according to NCI CTCAE 5.0) | From First dose to last patient progression or 6 months, whichever came first | An AE or SAE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Stage1：Incidence of adverse events SAE of single and multiple dose (according to NCI CTCAE 5.0) | From First dose to last patient progression or 6 months, whichever came first | An AE or SAE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Stage 1: The incidence and case number of DLT (Dose Limiting Toxicity) during observation period | From first dose up to 28 days | DLT is short for Dose Limiting Toxicity. dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. |
| Stage 2：Incidence of adverse events AE of single and multiple dose for AB011 combinate with XELOX or Gem/nab-P (according to NCI CTCAE 5.0) | From First dose to last patient progression or 12 months, whichever came first | An AE or SAE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Stage 2：Incidence of adverse events SAE of single and multiple dose for AB011 combinate with XELOX or Gem/nab-P (according to NCI CTCAE 5.0) | From First dose to last patient progression or 12 months, whichever came first | An AE or SAE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Stage 2: The incidence and case number of DLT (Dose Limiting Toxicity) during observation period | From first dose up to 21 days | DLT is short for Dose Limiting Toxicity. dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Pharmacokinetics: maximum concentration (Cmax) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6（dose increase stage), or cycle 8 (dose expansion stage), each cycle is 28 days, whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 2: Pharmacokinetics: maximum concentration (Cmax) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 1: Pharmacokinetics: half-life (T1/2) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6（dose increase stage), or cycle 8 (dose expansion stage), each cycle is 28 days, whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 2: Pharmacokinetics: half-life (T1/2) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 1: volume of distribution (Vd) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6（dose increase stage), or cycle 8 (dose expansion stage), each cycle is 28 days, whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 2: volume of distribution (Vd) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 1: Pharmacokinetics: Area Under Curve (AUC) with immunoanalytical method | Up to progression of disease after injection, or end of 6 cycle( each cycle is 28 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Efficacy: objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to progression of disease after injection, or 6 months( stage 1), 12 months (stage 2) whichever came first | These measure are defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1. |
| Efficacy: disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to progression of disease after injection, or 6 months( stage 1), 12 months (stage 2) whichever came first | These measure are defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1. |
| Efficacy: duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to progression of disease after injection, or 6 months( stage 1), 12 months (stage 2) whichever came first | These measure are defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1. |
| Efficacy: progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to progression of disease after injection, or 6 months( stage 1), 12 months (stage 2) whichever came first | These measure are defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1. |
| Efficacy: overall survival (OS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to progression of disease after injection, or 6 months( stage 1), 12 months (stage 2) whichever came first | These measure are defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1. |
| Immunogenicity | Up to 8 months (end of treatment) | Incidence of anti-drug antibodies |
| Stage 2: Pharmacokinetics: Area Under Curve (AUC) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 1: Pharmacokinetics: clearance rate (CL) with immunoanalytical method | Up to progression of disease after injection, or 6 cycle( dose increase), 8 cycle (dose extension), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 2: Pharmacokinetics: clearance rate (CL) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 1: Pharmacokinetics: minimum concentration (Cmin) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6（dose increase stage), or cycle 8 (dose expansion stage), each cycle is 28 days, whichever came first | AUC will be recorded from the PK serum samples collected. |
| Stage 2: Pharmacokinetics: minimum concentration (Cmin) with immunoanalytical method | Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first | AUC will be recorded from the PK serum samples collected. |
Countries
China
Outcome results
None listed