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 :
Active, not recruiting
First Posted : November 18, 2015
Last Update Posted : February 24, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced Malignancies | Drug: MBG453 Drug: PDR001 Drug: Decitabine | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 252 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 : | December 17, 2021 |
Estimated Study Completion Date : | December 20, 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 |
- 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 ]
- Overall response rate (ORR) per RECIST v1.1 [ Time Frame: 6.5 years ]
- Incidence of Dose limiting toxicities (DLTs) during the first cycle of treatment with single agent MBG453 [ Time Frame: 5 years ]
- 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 ]
- 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 ]
- 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 ]
- Best Overall Response (BOR) per RECIST v1.1 [ Time Frame: 6.5 years ]
- Maximum observed serum concentration (Cmax) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
- Presence and concentration of anti-MBG453 antibodies [ Time Frame: 6.5 years ]
- Expression of Programmed Death Ligand-1 (PD-L1) markers [ Time Frame: 6.5 years ]
- Tumor Infiltrating Lymphocytes (TIL) counts [ Time Frame: 6.5 years ]
- Overall survival [ Time Frame: 6.5 years ]
- Duration of Response (DOR) per RECIST v1.1 [ Time Frame: 6.5 years ]
- Progressive Free Survival (PFS) per RECIST v1.1 [ Time Frame: 6.5 years ]
- Progressive Free Survival per Immune-related Response Criteria (irRC) [ Time Frame: 6.5 years ]
- Overall Response Rate (ORR) per irRC [ Time Frame: 6.5 years ]
- Overall Response Rate (ORR) per RECIST v1.1 [ Time Frame: 6.5 years ]
- Time of maximum observed serum concentration (Tmax) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
- 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 ]
- 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 ]
- 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 ]
- Half-life (t1/2) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
- Clearance (CL) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
- Volume of distribution (V) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
- Accumulation ratio (AR) of MBG453 and PDR001 derived from serum concentration versus time [ Time Frame: 6.5 years ]
- Presence and concentration of anti-PDR001 antibodies [ Time Frame: 6.5 years ]
- Expression of immunological markers [ Time Frame: 6.5 years ]
- Expression of immune-related genes (RNA/protein) [ Time Frame: 6.5 years ]

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

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
United States, Maryland | |
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med Sidney Kimmel CCC | |
Baltimore, Maryland, United States, 21231 | |
United States, Massachusetts | |
Dana Farber Cancer Institute DFCI - Brookline | |
Boston, Massachusetts, United States, 02215 | |
United States, Texas | |
UT M.D Anderson Cancer Center | |
Houston, Texas, United States, 77030 | |
Cancer Therapy and Research Center UT Health Science Center | |
San Antonio, Texas, United States, 78229 | |
Canada, Ontario | |
Novartis Investigative Site | |
Toronto, Ontario, Canada, M5G 2C1 | |
Italy | |
Novartis Investigative Site | |
Milano, MI, Italy, 20141 | |
Novartis Investigative Site | |
Rozzano, MI, Italy, 20089 | |
Japan | |
Novartis Investigative Site | |
Kashiwa, Chiba, Japan, 277 8577 | |
Korea, Republic of | |
Novartis Investigative Site | |
Seoul, Korea, Republic of, 03080 | |
Netherlands | |
Novartis Investigative Site | |
Amsterdam, Netherlands, 1066 CX | |
Novartis Investigative Site | |
Leiden, Netherlands, 2300 RC | |
Singapore | |
Novartis Investigative Site | |
Singapore, Singapore, 169610 | |
Switzerland | |
Novartis Investigative Site | |
Geneve 14, Switzerland, CH 1211 | |
Taiwan | |
Novartis Investigative Site | |
Taipei, Taiwan, 10002 |
Study Chair: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
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 24, 2021 |
Last Verified: | February 2021 |
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Neoplasms Decitabine Antimetabolites, Antineoplastic Antimetabolites |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors |