Phase I-Ib/II Study of MBG453 as Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
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
- Advanced Malignancies
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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
- 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.
- Phase 1/Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- None (Open Label)
Dose escalation MBG453 alone
Dose escalation MBG453 in combination with PDR001
Dose Ranging group
Dose Expansion of MBG453 alone
Dose Expansion of MBG453 in combination with PDR001
Safety run in for MBG453 in combination with decitabine
- Novartis Pharmaceuticals
Study ContactNovartis Pharmaceuticals