Clinical Trials /

Safety and Efficacy of MBG453 as Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.

NCT02608268

Description:

The purpose of this first-in-human study of MBG453 is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MBG453 administered i.v. as a single agent or in combination with PDR001 in adult patients with advanced solid tumors

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of MBG453 as Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
  • Official Title: Phase I-Ib/II Open-label Multi-center Study of the Safety and Efficacy of MBG453 as Single Agent and in Combination With PDR001 in Adult Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CMBG453X2101
  • SECONDARY ID: 2015-002354-12
  • NCT ID: NCT02608268

Conditions

  • Advanced Malignancies

Interventions

DrugSynonymsArms
MBG453Dose escalation MBG453 alone
PDR001Dose escalation MBG453 in combination with PDR001

Purpose

The purpose of this first-in-human study of MBG453 is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MBG453 administered i.v. as a single agent or in combination with PDR001 in adult patients with advanced solid tumors

Trial Arms

NameTypeDescriptionInterventions
Dose escalation MBG453 aloneExperimental
  • MBG453
Dose escalation MBG453 in combination with PDR001Experimental
  • MBG453
  • PDR001
Dose Ranging groupExperimental
  • MBG453
  • PDR001
Dose Expansion of MBG453 aloneExperimental
  • MBG453
Dose Expansion of MBG453 in combination with PDR001Experimental
  • MBG453
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented advanced or metastatic solid tumors.

          -  Phase I-Ib part (including dose ranging part): Patients with advanced/metastatic solid
             tumors, with measurable or non-measurable disease as determined by RECIST v1.1, who
             have progressed despite standard therapy or are intolerant of standard therapy, or for
             whom no standard therapy exists and who did not receive prior anti-PD-1/PD-L1
             treatment.

          -  Phase II part (MBG453 single agent): Patients with advanced/metastatic solid tumors in
             the indication in which at least one confirmed PR or CR was seen during the dose
             escalation phase I part. Patients must have measurable disease as determined by RECIST
             v1.1, have progressed despite standard therapy or be intolerant to standard therapy.

          -  Phase II part (MBG453 in combination PDR001): Patients with advanced/metastatic tumors
             in the below selected indications, with at least one measurable lesion as determined
             by RECIST v1.1, who have received standard therapy and are intolerant of standard
             therapy or have progressed following their last prior therapy.:

               -  Melanoma (anti-PD-1/PD-L1 therapy naïve or pre-treated)

               -  Non small cell lung cancer (anti-PD-1/PD-L1 therapy naïve or pre-treated)

               -  Renal Cell Carcinoma (anti-PD-1/PD-L1 therapy naïve or pre-treated)

          -  Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy
             according to the treating institution's guidelines. Patient must be willing to undergo
             a new tumor biopsy at screening/baseline, and during therapy on the study.

        Exclusion Criteria:

          -  Presence of symptomatic central nervous system metastases.

          -  History of severe hypersensitivity reactions to other monoclonal antibodies.

          -  Human Immunodeficiency Virus, Hepatitis B Virus or Hepatitis C Virus infection.

          -  Active autoimmune disease or a documented history of autoimmune disease, including
             ulcerative colitis and Crohn's disease or any condition that requires systemic
             steroids.

          -  Systemic steroid therapy or any immunosuppressive therapy (≥10mg/day prednisone or
             equivalent).

          -  Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within
             4 weeks of initiation of study treatment.

          -  Pre-treatment with anti-CTLA4 antibodies in combination with any other antibody or
             drug specifically targeting T-cell co-stimulation or checkpoint pathway.

          -  Participation in an interventional, investigational non-immunotherapy study within 2
             weeks of the first dose of study treatment.

          -  Prior participation in an interventional, investigational cancer vaccine or
             immunotherapy study except for an anti-PD-1/PD-L1 study.

        Other inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of MBG453 alone and in combination with PDR001 as assessed by incidence and severity of adverse events
Time Frame:Up to 90 days after post study treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Best Overall Response (BOR) per RECIST v1.1
Time Frame:Every 8 weeks until week 40, and then every 12 weeks until end of disease progression follow-up. An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Maximum observed serum concentration (Cmax) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Presence and concentration of anti-MBG453 antibodies
Time Frame:On Day 1 of Cycle, 1, 2, 3, 4, 5 and 6 on Day 1 and End of treatment.An average of 2 years duration is expected.
Safety Issue:
Description:
Measure:Expression of Programmed Death Ligand-1 (PD-L1) markers
Time Frame:Screening (Day -28 to -1), after Cycle 3 (Day 84) and at the end of the study.An average of 2 years duration is expected.
Safety Issue:
Description:
Measure:Tumor Infiltrating Lymphocytes (TIL) counts
Time Frame:Screening (Day -28 to -1), after Cycle 3 (Day 84) and at the end of the study.An average of 2 years duration is expected.
Safety Issue:
Description:
Measure:Overall survival
Time Frame:From time of start treatment until the date of death.An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Duration of Response (DOR) per RECIST v1.1
Time Frame:Every 8 weeks until week 40, and then every 12 weeks until end of disease progression follow-up. An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Progressive Free Survival (PFS) per RECIST v1.1
Time Frame:Every 8 weeks until week 40, and then every 12 weeks until end of disease progression follow-up. An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Progressive Free Survival per Immune-related Response Criteria (irRC)
Time Frame:Every 8 weeks until week 40, and then every 12 weeks until end of disease progression follow-up. An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Overall Response Rate (ORR) per irRC
Time Frame:Every 8 weeks until week 40, and then every 12 weeks until end of disease progression follow-up. An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Overall Response Rate (ORR) per RECIST v1.1
Time Frame:Every 8 weeks until week 40, and then every 12 weeks until end of disease progression follow-up. An average of 1 year duration is expected.
Safety Issue:
Description:
Measure:Time of maximum observed serum concentration (Tmax) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Area under the concentration-time in one dosing interval (AUCtau) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Area under the curve up to the last measurable concentration (AUClast) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Half-life (t1/2) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Clearance (CL) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Volume of distribution (V) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Accumulation ratio (AR) of MBG453 and PDR001 derived from serum concentration versus time
Time Frame:19 timepoints up to an avarage of 1 year duration expected.
Safety Issue:
Description:
Measure:Presence and concentration of anti-PDR001 antibodies
Time Frame:On Day 1 of Cycle, 1, 2, 3, 4, 5 and 6 on Day 1 and End of treatment.An average of 2 years duration is expected.
Safety Issue:
Description:
Measure:Expression of immunological markers
Time Frame:Screening (Day -28 to -1), after Cycle 3 (Day 84) and at the end of the study.An average of 2 years duration is expected.
Safety Issue:
Description:
Measure:Expression of immune-related genes (RNA/protein)
Time Frame:Screening (Day -28 to -1), after Cycle 3 (Day 84) and at the end of the study.An average of 2 years duration is expected.
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Solid tumors
  • Melanoma
  • Non small cell lung cancer
  • NSCLC
  • Renal cell carcinoma
  • RCC
  • Phase I-Ib/II
  • MBG453
  • PDR001
  • Checkpoint inhibitor
  • PD-1
  • TIM-3

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