NCT03066648

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

Phase 1b, Multi-arm, Open-label Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 241 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a phase 1b, multi-arm, open-label study in patients with acute myeloid leukemia (AML) or intermediate or high risk myelodysplastic syndrome (MDS). Patients with myelodysplastic-myeloproliferative neoplasms (MDS/MPN), including chronic myelomonocytic leukemia (CMML) could also be enrolled. The study was comprised of six arms as described below. Arms 1-3 enrolled patients with newly diagnosed AML who were planned for non-intensive chemotherapy, relapsed/refractory (R/R) AML, or intermediate or high-risk MDS. * Arm 1: Evaluation of a fixed dose of the standard of care agent decitabine in combination with fixed dose PDR001. * Arm 2: Evaluation of a fixed dose of the standard of care agent decitabine in combination with escalating dose MBG453. * Arm 3: Evaluation of a fixed dose of the standard of care agent decitabine in combination with fixed dose PDR001 and escalating dose MBG453. Arms 4-5 enrolled patients with R/R AML or intermediate or high-risk MDS who had failed hypomethylating agent therapy. * Arm 4: Evaluation of an escalating dose of MBG453 * Arm 5: Evaluation of an escalating dose of MBG453 in combination with fixed dose PDR001 Arm 6 enrolled patients with newly diagnosed AML who were planned for non-intensive chemotherapy, or intermediate or high-risk MDS. * Arm 6: Evaluation of a fixed dose of the standard of care agent azacitidine in combination with an escalating dose of MBG453. Patients received the assigned treatment until disease progression, unacceptable toxicity, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient, lost to follow-up, death, or the study termination, whichever occurred first.

Conditions

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

Interventions

Type	Name	Description
DRUG	Decitabine	Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.
DRUG	PDR001	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.
DRUG	MBG453	MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer).
DRUG	Azacitidine	Azacitidine (5-azacytidine) is a cytidine nucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation

Timeline

• Start date: 2017-07-06
• Primary completion: 2023-09-08
• Completion: 2023-09-08
• First posted: 2017-02-28
• Last updated: 2025-05-18

Locations

11 sites across 8 countries: United States, Australia, Finland, France, Germany, Netherlands, Spain, United Kingdom

Regulatory

• FDA-regulated drug study