GR1405 Injection in Patients With Advanced Solid Tumor or Lymphoma

Study Overview
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Brief Summary
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This is a Phase I clinical study for evaluating the safety, pharmacokinetics, and preliminary efficacy of repeated doses, dose escalation of GR1405 injection in patients with advanced solid tumor or lymphoma

Detailed Description
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To evaluate the tolerability, safety, pharmacokinetics, and preliminary efficacy of GR1405 injection monotherapy in an open, non-controlled, escalating trial design in patients with advanced solid tumors or lymphomas. Four dose levels (3 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg) were evaluated at this stage.

Official Title
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A Phase I Clinical Study for Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Repeated Doses, Dose Escalation of GR1405 Injection in Patients With Advanced Solid Tumor or Lymphoma

Conditions
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Tumor, Solid, Lymphoma

Intervention / Treatment
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* Drug: GR1405 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with local advanced, recurrent or metastatic solid tumors confirmed by cytology or histology Lymphoma patients with pathological confirmation, and the above pat reients failed to standard treatment failure or had no standard treatment; Aged 18 to 75 years men and women; At least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors v1.1(RECIST v1.1 )(solid tumor) or Lugano 2014 criteria (lymphoma); Eastern Cooperative Oncology Group(ECOG)≤ 1 Female or male subjects of reproductive age and their mate are willing to take effective contraceptive measures for the entire treatment period and 6 months after the treatment; With sufficient organ and bone marrow function; At least 4 weeks after the last anti-tumor treatment before the first administration; The patient or his legal representative signs a written informed consent. Exclusion Criteria: Have experienced any National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) v4.03 or greater than 3 grade irAE during previous immunotherapy treatment; Has received any anti-PD-1(programmed death 1) or anti-PD-L1 antibody treatment; Subjects with other malignant tumors previously or concurrently ; Female patients with pregnancy or lactation; Women/men who have fertility refusal to adopt contraception during the trial period; Subjects with serious disease or complications, such as gastrointestinal bleeding, intestinal obstruction, intestinal paralysis, interstitial pneumonia, pulmonary fibrosis, renal failure, glaucoma, uncontrolled diabetes (CTCAE= 4.03: fasting blood glucose level ≥ 2), and with active infection; Had history of acute myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack 6 months before the screening ,grade 2 or above congestive heart failure devised by the New York Heart Association (NYHA); Subjects with symptomatic brain metastases or mental disorders; Subjects with abnormal levels of serum calcium, magnesium, potassium and have clinical significance; Subjects with history of immunodeficiency, including human immunodeficiency virus(HIV)-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation; Subjects with active hepatitis B (HBsAg and/or HBcAb positive, and HBV DNA titer in peripheral blood was greater than 1 x 103 IU/ml), and/or hepatitis C; Subjects who have alcohol addiction and/or drug abuse; Subjects with bleeding or coagulation dysfunction in the past 3 months (Prothrombin time(PT)>1.5×upper limit of normal(ULN); activated partial thromboplastin time(APTT)>1.5×ULN; thrombin time(TT)>1.5×ULN); Subjects with allergic constitution or allergic to known components of the drug; Those who received other clinical trial drug therapy within 1 month before the first administration; Receive a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or during the study period; Other subjects judged by the investigator to be ineligible for enrollment in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GR1405 injection 3 mg/kg<br>According to the patient's weight, the dose of this group is 3mg/kg. | Drug: GR1405 injection<br>* Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.<br>* Other names: PD-L1 monoclonal antibody;|
| Experimental: GR1405 injection 10 mg/kg<br>According to the patient's weight, the dose of this group is 10mg/kg. | Drug: GR1405 injection<br>* Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.<br>* Other names: PD-L1 monoclonal antibody;|
| Experimental: GR1405 injection 20 mg/kg<br>According to the patient's weight, the dose of this group is 20mg/kg. | Drug: GR1405 injection<br>* Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.<br>* Other names: PD-L1 monoclonal antibody;|
| Experimental: GR1405 injection 30 mg/kg<br>According to the patient's weight, the dose of this group is 30mg/kg. | Drug: GR1405 injection<br>* Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.<br>* Other names: PD-L1 monoclonal antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | Maximum tolerated dose of GR1405 injection | 2 weeks | 
| Adverse Events | Number of Participants With Treatment-Emergent Adverse Events as Assessed by CTCAE v4.03 | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) | the maximum exposure to a biologically active physica | Approximately 2 years | 
| Duration of response (DOR) | DOR by RECIST v. 1.1 or Lugano 2014, the time between the initial response to therapy and subsequent disease progression or relapse | Approximately 3 years | 
| Objective Response Rate(ORR) | Objective Response Rate(ORR) by RECIST v. 1.1 or Lugano 2014, ORR=complete response(CR) + partial response(PR) | Approximately 3 years | 
| Progression free survival(PFS) | Progression free survival(PFS) by RECIST v. 1.1 or Lugano 2014, a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works | Approximately 3 years | 
| Immunogenicity | the ability to elicit an immune response of GR1405 injection, | Approximately 3 years | 
| Recommended dose for Phase II trial(RP2D) | The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced dose-limiting toxicity(DLT) attributable to the study drug. The MTD will be the RP2D | Approximately 3 years | 
| AUC0-t | Area under the curve in the period from 0 to t | Approximately 2 years | 
| AUC0-∞ | Area under the curve in the period from 0 to ∞ | Approximately 2 years | 
| AUCss | Area under the curve of Steady-State Plasma Concentrations | Approximately 2 years | 
| T max | the time of occurrence of peak drug concentration | Approximately 2 years | 
| t 1/2 | the time of half-life of the drug | Approximately 2 years | 
| apparent volume of distribution (Vz) | the volume of fluid that would be required to contain the amount of drug in the body | Approximately 2 years | 
| clearance(CL) | the rate of elimination of the drug in vivo | Approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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programmed death ligand-1 (PD-L1)