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Phase I-Ib/II Study of MBG453 as Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02608268
Recruitment Status : Recruiting
First Posted : November 18, 2015
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or decitabine in adult patients with advanced solid tumors

Condition or disease Intervention/treatment Phase
Advanced Malignancies Drug: MBG453 Drug: PDR001 Drug: Decitabine Phase 1 Phase 2

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Study Type : Interventional
Estimated Enrollment : 269 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 23, 2015
Estimated Primary Completion Date : October 14, 2021
Estimated Study Completion Date : October 15, 2021


Arm Intervention/treatment
Experimental: Dose escalation MBG453 alone Drug: MBG453
anti human TIM-3 monoclonal antibody

Experimental: Dose escalation MBG453 in combination with PDR001 Drug: MBG453
anti human TIM-3 monoclonal antibody

Drug: PDR001
anti-human PD-1 monoclonal antibody

Experimental: Dose Ranging group Drug: MBG453
anti human TIM-3 monoclonal antibody

Drug: PDR001
anti-human PD-1 monoclonal antibody

Experimental: Dose Expansion of MBG453 alone Drug: MBG453
anti human TIM-3 monoclonal antibody

Experimental: Dose Expansion of MBG453 in combination with PDR001 Drug: MBG453
anti human TIM-3 monoclonal antibody

Drug: PDR001
anti-human PD-1 monoclonal antibody

Experimental: Safety run in for MBG453 in combination with decitabine Drug: Decitabine
commercially available chemotherapy




Primary Outcome Measures :
  1. Safety and tolerability of MBG453 alone and in combination with PDR001 or in combination with decitabine as assessed by incidence and severity of adverse events [ Time Frame: 6.5 years ]
  2. Overall response rate (ORR) per RECIST v1.1 [ Time Frame: 6.5 years ]
  3. Incidence of Dose limiting toxicities (DLTs) during the first cycle of treatment with single agent MBG453 [ Time Frame: 5 years ]
  4. Incidence of DLTs during the first and second cycle of treatment with MBG453 in combination with PDR001 or in combination with decitabine [ Time Frame: 6.5 years ]
  5. Tolerability of MBG453 alone and in combination with PDR001 or in combination with decitabine, as assessed by number of dose changes [ Time Frame: 6.5 years ]
  6. Tolerability of MBG453 alone and in combination with PDR001 or in combination with decitabine, as assessed by number of dose interruptions [ Time Frame: 6.5 years ]

Secondary Outcome Measures :
  1. Best Overall Response (BOR) per RECIST v1.1 [ Time Frame: 6.5 years ]
  2. Maximum observed serum concentration (Cmax) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  3. Presence and concentration of anti-MBG453 antibodies [ Time Frame: 6.5 years ]
  4. Expression of Programmed Death Ligand-1 (PD-L1) markers [ Time Frame: 6.5 years ]
  5. Tumor Infiltrating Lymphocytes (TIL) counts [ Time Frame: 6.5 years ]
  6. Overall survival [ Time Frame: 6.5 years ]
  7. Duration of Response (DOR) per RECIST v1.1 [ Time Frame: 6.5 years ]
  8. Progressive Free Survival (PFS) per RECIST v1.1 [ Time Frame: 6.5 years ]
  9. Progressive Free Survival per Immune-related Response Criteria (irRC) [ Time Frame: 6.5 years ]
  10. Overall Response Rate (ORR) per irRC [ Time Frame: 6.5 years ]
  11. Overall Response Rate (ORR) per RECIST v1.1 [ Time Frame: 6.5 years ]
  12. Time of maximum observed serum concentration (Tmax) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  13. 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: 6.5 years ]
  14. Area under the concentration-time in one dosing interval (AUCtau) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  15. Area under the curve up to the last measurable concentration (AUClast) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  16. Half-life (t1/2) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  17. Clearance (CL) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  18. Volume of distribution (V) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  19. Accumulation ratio (AR) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
  20. Presence and concentration of anti-PDR001 antibodies [ Time Frame: 6.5 years ]
  21. Expression of immunological markers [ Time Frame: 6.5 years ]
  22. Expression of immune-related genes (RNA/protein) [ Time Frame: 6.5 years ]


Information from the National Library of Medicine

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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:

  • 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.
  • For MBG453 in combination with decitabine: anti-PD-1/PD-L1 therapy naïve SCLC patients who have failed no more than two lines of standard chemotherapy including topotecan

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.
  • For MBG453 in combination with decitabine: Hypersensitivity to decitabine or to any of the excipients, listed in decitabine country specific label

Other inclusion/exclusion criteria may apply.


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): NCT02608268


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Maryland
Novartis Investigative Site Recruiting
Baltimore, Maryland, United States, 21231
Contact: Bhavika Patel       bpatel5@jhmi.edu   
Principal Investigator: Patrick Forde         
United States, Massachusetts
Novartis Investigative Site Recruiting
Boston, Massachusetts, United States, 02215
Contact: Natasha Isaac    617-582-7116    Nisaac1@partners.org   
Principal Investigator: F Stephen Hodi         
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Contact: Lacey McQuinn    713-563-9033    lmcquinn@mdanderson.org   
Principal Investigator: Aung Naing         
Novartis Investigative Site Recruiting
San Antonio, Texas, United States, 78229
Contact: Kathleen Rodriguez    210-450-3838    rodriguezk3@uthscsa.edu   
Principal Investigator: John Sarantopoulos         
Canada, Ontario
Novartis Investigative Site Active, not recruiting
Toronto, Ontario, Canada, M6G 1Z5
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Kashiwa, Chiba, Japan, 277 8577
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site Recruiting
Leiden, Netherlands, 2300 RC
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Switzerland
Novartis Investigative Site Recruiting
Geneve 14, Switzerland, CH 1211
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02608268    
Other Study ID Numbers: CMBG453X2101
2015-002354-12 ( EudraCT Number )
First Posted: November 18, 2015    Key Record Dates
Last Update Posted: February 10, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Solid tumors
Non small cell lung cancer
Melanoma
NSCLC
Renal cell carcinoma
RCC
Phase I-Ib/II
MBG453
PDR001
Checkpoint inhibitor
PD-1
TIM-3
Additional relevant MeSH terms:
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Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors