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Trial record 1 of 1 for:    APD-SMG-I
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A Phase 1 Study of GNR-051 in Subjects With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT04544748
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : September 22, 2021
Sponsor:
Information provided by (Responsible Party):
AO GENERIUM

Brief Summary:
It is a Phase 1 Multicenter Open-Label Multi-Cohort Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of GNR-051 in Subjects with Advanced Solid Malignancies.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma (RCC), Malignant Melanoma (MEL) Biological: GNR-051 Phase 1

Detailed Description:
GNR-051 is a monoclonal antibody, targeting the Programmed Death-1 (PD-1) membrane receptor on T lymphocytes and other cells of the immune system. The anti-PD-1 antibody, preventing the binding of the PD-1 receptor with the ligands PD-L1 and PD-L2, reactivates the pool of tumor-specific cytotoxic T-lymphocytes in the tumor microenvironment and, thus, reactivates the antitumor immunity. GNR-051 is able to block the signaling molecule PD-1, which suppresses the antitumor immune response, for the treatment of cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Open-Label Multi-Cohort Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of GNR-051 (GENERIUM JSC, Russia) in Subjects With Solid Advanced Malignancies
Actual Study Start Date : July 22, 2020
Estimated Primary Completion Date : April 22, 2024
Estimated Study Completion Date : June 15, 2024


Arm Intervention/treatment
Cohort 1
GNR-051 (0.1 mg/kg)
Biological: GNR-051
Anti-PD1 monoclonal antibody

Cohort 2
GNR-051 (0.3 mg/kg)
Biological: GNR-051
Anti-PD1 monoclonal antibody

Cohort 3
GNR-051 (1 mg/kg)
Biological: GNR-051
Anti-PD1 monoclonal antibody

Cohort 4
GNR-051 (3 mg/kg)
Biological: GNR-051
Anti-PD1 monoclonal antibody

Cohort 5
GNR-051 (10 mg/kg)
Biological: GNR-051
Anti-PD1 monoclonal antibody




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 28 Days ]
    Tolerability of GNR-051

  2. Number of participants with dose-limiting toxicity (DLT) [ Time Frame: 28 Days ]
    Tolerability of GNR-051

  3. Laboratory tests [ Time Frame: 36 Months ]
    Safety profile of GNR-051; All adverse events (CTCAE 5.0)

  4. Vital signs [ Time Frame: 36 Months ]
    Safety profile of GNR-051; All adverse events (CTCAE 5.0)

  5. Physical examination [ Time Frame: 36 Months ]
    Safety profile of GNR-051; All adverse events (CTCAE 5.0)

  6. 12-lead electrocardiogram [ Time Frame: 36 Months ]
    Safety profile of GNR-051; All adverse events (CTCAE 5.0)

  7. ECOG assessment [ Time Frame: 36 Months ]
    Safety profile of GNR-051; All adverse events (CTCAE 5.0)

  8. Antidrug antibody [ Time Frame: 36 Months ]
    Safety profile of GNR-051; All adverse events (CTCAE 5.0)


Secondary Outcome Measures :
  1. GNR-051 Serum Concentration [ Time Frame: 6 Months ]
    Pharmacokinetic parameters GNR-051

  2. Cmax - Maximum serum concentration after the 1st administration [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  3. Cmin - Minimum serum concentration after the 1st administration [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  4. Tmax - Time to peak serum concentration after the 1st administration [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  5. t½ - Half-life after the 1st administration, [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  6. CL - Clearance after the 1st administration [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  7. AUC0-t - Area Under the Curve after the 1st administration [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  8. Tmax, SS - Time to peak serum concentration at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  9. CSS - serum concentration at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  10. Cmax, SS - Maximum serum concentration at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  11. CLSS - Clearance at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  12. Cmin, SS - serum concentration at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  13. Vd, SS - Volume of distribution at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  14. CAUCτ 0-t - Area under the concentration time-curves from zero to the end of the dosing interval at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  15. t½,ss - Half-life at steady state [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  16. AUC0-∞ - Area under the concentration time-curves from time zero to infinity after last administration [ Time Frame: 36 Months ]
    PharmacoCkinetic parameters

  17. Accumulation index (Rac; steady-state AUC0-τ/single-dose AUC0-τ) [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  18. Time to reach steady state - elimination half-life [ Time Frame: 6 Months ]
    Pharmacokinetic parameters

  19. PD-1 receptor occupancy rate (%) in peripheral blood mononuclear cells (PBMCs) [ Time Frame: 6 Months ]
    Pharmacodynamic parameters GNR-051

  20. Objective Response Rate (ORR) [ Time Frame: 36 Months ]
    Objective Response Rate (ORR) - best response of complete remission (CR) or partial remission (PR) according to RECIST 1.1 and IRECIST

  21. Best objective response rate (complete response (CR) + partial response (PR)) [ Time Frame: 36 Months ]
    Best objective response rate (complete response (CR) + partial response (PR)) according to RECIST 1.1 and IRECIST

  22. Progression-Free Survival (PFS) [ Time Frame: 36 Months ]
    Progression-Free Survival (PFS) - time from 1st dose administration to progression according to RECIST 1.1 or until death from any cause

  23. Disease Control Rate (DCR) [ Time Frame: 36 Months ]
    Disease Control Rate (DCR) - percentage of patients who have achieved complete response, partial response and stable disease

  24. Best Overall Response (BOR) [ Time Frame: 36 Months ]
    Best Overall Response (BOR) - the best response recorded from the 1st dose administration until the disease progression

  25. Duration of response (DoR) [ Time Frame: 36 Months ]
    Duration of response - the length of time that a tumor continues to respond to treatment without the cancer growing or spreading

  26. Overall Survival (OS) [ Time Frame: 36 Months ]
    Overall Survival (OS) - time from enrollment to the date of death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Signed Informed Consent Form and the subject's ability to follow the Protocol requirements;
  • Age: 18 years and older at the signing of the informed consent;
  • Histologically confirmed metastatic solid malignant tumors (non-small cell lung cancer, renal cell carcinoma, melanoma), refractory or recurrent after one or more courses of previous therapy and not subject to surgical treatment and radiation therapy. Melanoma - regardless of the presence and success of previous treatment;
  • ECOG performance status ≤ 2;
  • At least one RESICT 1.1-defined measurable target lesion;
  • Completion of the previous drug treatment of the underlying disease (if applicable) at least 28 days before the first administration of GNR-051;
  • Resolution or stabilization of toxicity manifestations of previous radiation or chemotherapy.

Exclusion Criteria:

  • Prior treatment with anti-CTLA4 and/or anti-PD-1/PD-L1/PD-L2 agents;
  • Hypersensitivity to any of the components of GNR-051;
  • Progression (growth of previous, appearance of new) metastases in the brain and meninges, identified by CT or MRI, in a period of less than 56 days before the first administration of GNR-051; worsening of neurological symptoms in a patient with metastases in the brain or meninges within a period of less than 28 days before the first administration of GNR-051; or continued treatment of metastases in the brain or meninges with glucocorticosteroids (GCS) for a period of less than 14 days before the first administration of GNR-051 (except for a maintenance daily dose of GCS equivalent to 10 mg of prednisolone);
  • Inability to conduct a biopsy according to the protocol;
  • Left ventricular ejection fraction (LVEF) <50% (EchoCG);
  • The need to use anticancer drugs, other than the investigated one, for at least 3 months after the first administration of the drug;
  • Patients who need radiotherapy or surgical therapy;
  • Previous radiotherapy ended <28 days before the first dose administration;
  • Previous stereotactic radiation therapy ended <14 days before the first dose administration;
  • Therapeutic use of radiopharmaceuticals ≤56 days prior to first dose administration;
  • Patients who have received another experimental drug (not registered in Russia) within 28 days or 5 half-lives of the experimental drug before the first administration GNR-051;
  • Patients who have received vaccines against infectious diseases (eg influenza virus) within 28 days before the first administration of the drug;
  • Patients who have received narcotic analgesics <14 days before the first administration of GNR-051;
  • Surgery with general anesthesia <28 days before the first administration of GNR-051.
  • Surgery with regional / epidural anesthesia <72 hours and / or not all post-anesthetic AEs resolved before the first administration of GNR-051;
  • Laboratory parameters:

    • Absolute leukocyte count <2000 / μL;
    • Absolute neutrophil count <1500 / μL;
    • Absolute platelet count <100 × 103 / μL;
    • Hemoglobin level <9.0 g / dL;
    • Creatinine> 2 mg / dL;
    • AST> 2.5 × the upper limit of normal (ULN) in the absence of liver metastases, or> 5 × ULN with the liver metastases;
    • ALT > 2.5 × ULN in the absence of liver metastases, or> 5 × ULN with the liver metastases;
    • Total bilirubin> 2 × ULN;
  • Systemic autoimmune diseases (including but not limited to SLE, Crohn's disease, ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, etc.);
  • Concomitant cancer (except for basal or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, prostate, or breast);
  • Patients who need therapy with corticosteroids or other immunosuppressants;
  • Systemic therapy with corticosteroids or immunosuppressants for ≤7 days before the first administration GNR-051;
  • Any other concomitant condition (e.g., medical condition, mental disorders, alcohol/drug abuse) that constitutes an unacceptable risk to the patient's health during the investigational therapy or prevents a patient from following the Protocol procedures;
  • Active HBV/HCV/HIV infection;
  • Pregnant or lactating female;
  • Patients with reproductive potential who do not agree to practice acceptable methods of birth control throughout the entire trial period, starting from signing the informed consent and up to 6 months after the last dose of GNR-051;
  • Simultaneous participation in other clinical trials.

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): NCT04544748


Contacts
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Contact: Svetlana B. Korotkova, MD, PhD +7 9166816567 sbkorotkova@generium.ru
Contact: Oksana A. Markova, MD, MSc +7 9854418959 oamarkova@generium.ru

Locations
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Russian Federation
SAHI "Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Tatarstan" Not yet recruiting
Kazan, Russian Federation, 420029
SBHI "Leningrad Regional Clinical Oncology Dispensary" Not yet recruiting
Leningrad Region, Russian Federation, 188663
FSBI "N.N. Blokhin National Medical Research Center of Oncology"of the Ministry of Health of the Russian Federation Not yet recruiting
Moscow, Russian Federation, 115478
FSBI "Russian Scientific Center of Roentgenoradiology" of the Ministry of Health of the Russian Federation Not yet recruiting
Moscow, Russian Federation, 117997
FSAEI HE "I.M. Sechenov First Moscow State Medical University" of the Ministry of Health of Russian Federation Recruiting
Moscow, Russian Federation, 119991
JSC "MEDSI" Group of Companies" Not yet recruiting
Moscow, Russian Federation, 123056
FSII "Treatment and Rehabilitation Center" of the Ministry of Health of the Russian Federation Not yet recruiting
Moscow, Russian Federation, 125367
FSBI "N.N. Petrov National Medical Research Center of Oncology" of the Ministry of Healthcare of the Russian Federation Not yet recruiting
Moscow, Russian Federation, 197758
JSC "Modern Medical Technologies" Not yet recruiting
Saint Petersburg, Russian Federation, 190013
FSAEI HE "I.P. Pavlov First Saint Petersburg State Medical University" of the Ministry of Health of the Russian Federation Not yet recruiting
Saint Petersburg, Russian Federation, 197022
SBHI "St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological) Not yet recruiting
Saint Petersburg, Russian Federation, 197758
LLC "Tentanda Via" Not yet recruiting
Saint Petersburg, Russian Federation, 198035
Sponsors and Collaborators
AO GENERIUM
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Responsible Party: AO GENERIUM
ClinicalTrials.gov Identifier: NCT04544748    
Other Study ID Numbers: APD-SMG-I
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AO GENERIUM:
Neoplasms
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Renal Cell
Urologic Neoplasms
Lung Neoplasms
Antineoplastic Agents, Immunological
Kidney Neoplasms
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases