Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS

NCT03066648 | Completed Phase 1 FDA Drug

• 2 other identifiers: CPDR001X21052016-005060-33
• Study Type: interventional
• Target: 241
• Locations: 8 countries
• Sites: 11

Brief Summary

To characterize the safety and tolerability of 1) MBG453 as a single agent or in combination with PDR001 or 2) PDR001 and/or MBG453 in combination with decitabine or azacitidine in AML and intermediate or high- risk MDS patients, and to identify recommended doses for future studies.

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Preleukemia; Bone Marrow Diseases; Hematologic Diseases; Chronic Myelomonocytic Leukemia

Keywords

Acute Myeloid Leukemia; Myelodysplastic syndromes; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (4)

• Safety of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine or azacitidine.

  Incidence and severity of AEs and SAEs

  24 months

• Incidence of Dose Limiting Toxicities (DLTs)

  The incidence of DLTs during the first two cycles of treatment with MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine.

  2 months

• Incidence of Dose Limiting Toxicities (DLTs)

  The incidence of DLTs during the first cycle of MBG453 single agent treatment or during the first two cycles of treatment with MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine.

  1 month

• Tolerability of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine or azacitidine.

  Incidence and severity of AEs and SAEs

  24 months

Secondary Outcomes (10)

• AUC of PDR001, MBG453, decitabine and azacitidine.

  24 months

• Cmax of PDR001, MBG453, decitabine and azacitidine

  24 months

• Tmax of PDR001, MBG453, decitabine and azacitidine

  24 months

• Half-life of PDR001, MBG453, decitabine and azacitidine

  24 months

• Overall Response Rate (ORR)

  24 months

Study Arms (6)

Decitabine and PDR001

EXPERIMENTAL

Decitabine in combination with PDR001

Drug: Decitabine; Drug: PDR001

Decitabine and MBG453

EXPERIMENTAL

Decitabine in combination with MBG453

Drug: Decitabine; Drug: MBG453

Decitabine, PDR001 and MBG453

EXPERIMENTAL

Decitabine in combination with PDR001 and MBG453

Drug: Decitabine; Drug: PDR001; Drug: MBG453

MBG453

EXPERIMENTAL

MBG453 alone

Drug: MBG453

MBG453 and PDR001

EXPERIMENTAL

MBG453 in combination with PDR001

Drug: PDR001; Drug: MBG453

Azacitidine and MBG453

EXPERIMENTAL

Azacitidine in combination with MBG453

Drug: MBG453; Drug: Azacitidine

Interventions

Decitabine DRUG

Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.

Also known as: 5-aza-2'-deoxycytidine

Decitabine and MBG453; Decitabine and PDR001; Decitabine, PDR001 and MBG453

PDR001 DRUG

PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2.

Also known as: spartalizumab

Decitabine and PDR001; Decitabine, PDR001 and MBG453; MBG453 and PDR001

MBG453 DRUG

MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer).

Also known as: sabatolimab

Azacitidine and MBG453; Decitabine and MBG453; Decitabine, PDR001 and MBG453; MBG453; MBG453 and PDR001

Azacitidine DRUG

Azacitidine (5-azacytidine) is a cytidine nucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation

Also known as: 5-azacytidine

Azacitidine and MBG453

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures
• Male or female patients ≥ 18 years of age who present with one of the following:
• Arms 1-3:
• Relapsed/refractory AML following ≥1 prior therapies who have relapsed or exhibited refractory disease (primary failure) and are deemed by the investigator not to be candidates for standard therapy, including re-induction with cytarabine or other established chemotherapy regimens for patients with AML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
• Newly diagnosed AML patients who are suitable for treatment with decitabine (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
• Intermediate or high risk MDS or MDS/MPN including CMML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
• Arms 4-5:
• Refractory / relapsed AML following ≥1 prior therapies (Arms 4a \& 5a)
• Intermediate or high risk MDS or MDS/MPN including CMML who have failed hypomethylating agent therapy (Arms 4b \& 5b) (Note: hypomethylating agent failure is defined as progressive disease on hypomethylating agent therapy or lack of clinically meaningful response as deemed by investigator after at least 4 cycles of hypomethylating agent therapy.)
• Arm 6:
• Newly diagnosed AML patients who are suitable for treatment with azacitidine (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded) (Arm 6a)
• Intermediate or high-risk MDS or MDS/MPN including CMML (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded) (Arm 6b)
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and be willing to undergo a bone marrow aspirate and/biopsy at screening, during and at the end of therapy on this study. Exceptions may be considered after documented discussion with Novartis.
• Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by the investigator and as per local decitabine package insert.

You may not qualify if:

• Arms 1-3 or Arm 6: Patients who have received prior hypomethylating agent treatment for AML or MDS.
• Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur should not be excluded.
• History of, or current drug-induced interstitial lung disease or pneumonitis grade ≥ 2.
• Patients who discontinued prior PD-1 or PD-L1 directed therapy due to a treatment related toxicity should not be included in the PDR001 containing arms of the study. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
• Systemic antineoplastic therapy (including cytotoxic chemotherapy, alphainterferon, kinase inhibitors or other targeted small molecules, and toxinimmunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment.
• Systemic chronic corticosteroid therapy (\>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Oregon Health Sciences University Main Center

Portland, Oregon, 97239, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Helsinki, FIN 00290, Finland

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Jena, 07740, Germany

Location

Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Cardiff, CF4 4XN, United Kingdom

Location

Related Links

• Study Results
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Preleukemia; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Myelomonocytic, Chronic

Interventions

Decitabine; spartalizumab; sabatolimab; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2017
• First Posted: February 28, 2017
• Study Start: July 6, 2017
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); FR (1); AU (1); ES (1); FI (1); DE (2); GB (1); NL (1)