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GR1405 Injection in Patients With Advanced Solid Tumor or Lymphoma

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ClinicalTrials.gov Identifier: NCT03731390
Recruitment Status : Not yet recruiting
First Posted : November 6, 2018
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
Shi Yuankai, 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

Condition or disease Intervention/treatment Phase
Tumor, Solid Lymphoma Drug: GR1405 injection Phase 1

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 Type : Interventional
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: GR1405 injection 3 mg/kg
According to the patient's weight, the dose of this group is 3mg/kg.
Drug: GR1405 injection
Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.
Other Name: PD-L1 monoclonal antibody

Experimental: GR1405 injection 10 mg/kg
According to the patient's weight, the dose of this group is 10mg/kg.
Drug: GR1405 injection
Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.
Other Name: PD-L1 monoclonal antibody

Experimental: GR1405 injection 20 mg/kg
According to the patient's weight, the dose of this group is 20mg/kg.
Drug: GR1405 injection
Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.
Other Name: PD-L1 monoclonal antibody

Experimental: GR1405 injection 30 mg/kg
According to the patient's weight, the dose of this group is 30mg/kg.
Drug: GR1405 injection
Intravenous administration according to the patient's weight. All dose groups were administered once every 2 weeks.
Other Name: PD-L1 monoclonal antibody




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 2 weeks ]
    Maximum tolerated dose of GR1405 injection

  2. Adverse Events [ Time Frame: Approximately 3 years ]
    Number of Participants With Treatment-Emergent Adverse Events as Assessed by CTCAE v4.03


Secondary Outcome Measures :
  1. maximum concentration (Cmax) [ Time Frame: Approximately 2 years ]
    the maximum exposure to a biologically active physica

  2. Duration of response (DOR) [ Time Frame: 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

  3. Objective Response Rate(ORR) [ Time Frame: Approximately 3 years ]
    Objective Response Rate(ORR) by RECIST v. 1.1 or Lugano 2014, ORR=complete response(CR) + partial response(PR)

  4. Progression free survival(PFS) [ Time Frame: 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

  5. Immunogenicity [ Time Frame: Approximately 3 years ]
    the ability to elicit an immune response of GR1405 injection,

  6. Recommended dose for Phase II trial(RP2D) [ Time Frame: 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

  7. AUC0-t [ Time Frame: Approximately 2 years ]
    Area under the curve in the period from 0 to t

  8. AUC0-∞ [ Time Frame: Approximately 2 years ]
    Area under the curve in the period from 0 to ∞

  9. AUCss [ Time Frame: Approximately 2 years ]
    Area under the curve of Steady-State Plasma Concentrations

  10. T max [ Time Frame: Approximately 2 years ]
    the time of occurrence of peak drug concentration

  11. t 1/2 [ Time Frame: Approximately 2 years ]
    the time of half-life of the drug

  12. apparent volume of distribution (Vz) [ Time Frame: Approximately 2 years ]
    the volume of fluid that would be required to contain the amount of drug in the body

  13. clearance(CL) [ Time Frame: Approximately 2 years ]
    the rate of elimination of the drug in vivo



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03731390


Contacts
Contact: yuankai Shi, M.D. 86 010-87788293 syuankaipumc@126.com

Locations
China
Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, China
Sponsors and Collaborators
Chinese Academy of Medical Sciences
Investigators
Principal Investigator: yuankai Shi, M.D. Chinese Academy of Medical Sciences

Publications:

Responsible Party: Shi Yuankai, Vice-president, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT03731390     History of Changes
Other Study ID Numbers: GR1405-002
First Posted: November 6, 2018    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shi Yuankai, Chinese Academy of Medical Sciences:
programmed death ligand-1 (PD-L1)

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases