GR1405 Injection in Patients With Advanced Solid Tumor or Lymphoma

Phase 1

• Conditions: Tumor, Solid; Lymphoma
• Interventions: Drug: GR1405 injection

• Registration Number: NCT03731390
• Lead Sponsor: Chinese Academy of Medical Sciences

Brief Summary

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

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.

Study Timeline

• Status Verified: 2018-11
• Study Start: 2018-11
• Study First Submitted: 2018-11-02
• Study First Submitted QC: 2018-11-04
• Last Update Submitted: 2018-11-04
• Study First Posted: 2018-11-06
• Last Update Posted: 2018-11-06
• Primary Completion: 2019-10
• Study Completion: 2021-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. 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;
2. Aged 18 to 75 years men and women;
3. 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);
4. Eastern Cooperative Oncology Group(ECOG)≤ 1
5. 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;
6. With sufficient organ and bone marrow function;
7. At least 4 weeks after the last anti-tumor treatment before the first administration;
8. The patient or his legal representative signs a written informed consent.

Exclusion Criteria

1. 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;
2. Has received any anti-PD-1(programmed death 1) or anti-PD-L1 antibody treatment;
3. Subjects with other malignant tumors previously or concurrently ;
4. Female patients with pregnancy or lactation;
5. Women/men who have fertility refusal to adopt contraception during the trial period;
6. 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;
7. 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);
8. Subjects with symptomatic brain metastases or mental disorders;
9. Subjects with abnormal levels of serum calcium, magnesium, potassium and have clinical significance;
10. Subjects with history of immunodeficiency, including human immunodeficiency virus(HIV)-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation;
11. 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;
12. Subjects who have alcohol addiction and/or drug abuse;
13. 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);
14. Subjects with allergic constitution or allergic to known components of the drug;
15. Those who received other clinical trial drug therapy within 1 month before the first administration;
16. Receive a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or during the study period;
17. Other subjects judged by the investigator to be ineligible for enrollment in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GR1405 injection 3 mg/kg	GR1405 injection	According to the patient's weight, the dose of this group is 3mg/kg.
GR1405 injection 10 mg/kg	GR1405 injection	According to the patient's weight, the dose of this group is 10mg/kg.
GR1405 injection 20 mg/kg	GR1405 injection	According to the patient's weight, the dose of this group is 20mg/kg.
GR1405 injection 30 mg/kg	GR1405 injection	According to the patient's weight, the dose of this group is 30mg/kg.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Duration of response (DOR)	Approximately 3 years	DOR by RECIST v. 1.1 or Lugano 2014, the time between the initial response to therapy and subsequent disease progression or relapse
Objective Response Rate(ORR)	Approximately 3 years	Objective Response Rate(ORR) by RECIST v. 1.1 or Lugano 2014, ORR=complete response(CR) + partial response(PR)
Recommended dose for Phase II trial(RP2D)	Approximately 3 years	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
apparent volume of distribution (Vz)	Approximately 2 years	the volume of fluid that would be required to contain the amount of drug in the body
Progression free survival(PFS)	Approximately 3 years	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
t 1/2	Approximately 2 years	the time of half-life of the drug
maximum concentration (Cmax)	Approximately 2 years	the maximum exposure to a biologically active physica
Immunogenicity	Approximately 3 years	the ability to elicit an immune response of GR1405 injection,
AUC0-t	Approximately 2 years	Area under the curve in the period from 0 to t
AUCss	Approximately 2 years	Area under the curve of Steady-State Plasma Concentrations
AUC0-∞	Approximately 2 years	Area under the curve in the period from 0 to ∞
T max	Approximately 2 years	the time of occurrence of peak drug concentration
clearance(CL)	Approximately 2 years	the rate of elimination of the drug in vivo

Trial Locations

Locations (1)

Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; 🇨🇳 Beijing, China