NCT02608268

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

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 252 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this first-in-human study of MBG453 was 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

Detailed description

This study was a first in human (FIH), open-label, Phase I-Ib/II, multi-center study which consisted of a Phase I dose escalation part of sabatolimab (MBG453) as single agent, and a Phase Ib dose escalation part of sabatolimab in combination with spartalizumab (PDR001) that commenced after two cohorts in the dose escalation with single agent were completed. Once the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of sabatolimab as single agent and in combination with spartalizumab was achieved, a dose ranging part and a Phase II part started. • Phase I dose escalation part (sabatolimab single agent): In the Phase I part of the study, cohorts of subjects were treated with sabatolimab as single agent either every 2 weeks (Q2W) or every 4 weeks (Q4W) until the MTD was reached or a lower RP2D was established. The sabatolimab single agent dose escalation part in Japan ran separately in order to ensure that the safety and pharmacokinetics (PK) profiles of single-agent sabatolimab are adequately characterized in Japanese patients. If the recommended dose of single agent sabatolimab in Japanese patients was the same as in the rest of the world (ROW) patients, then patients enrolled in Japan were to be recruited into the other parts of the study. • Phase Ib dose escalation part (sabatolimab in combination with spartalizumab): The combination Phase Ib part of the study was to be commenced after at least two cohorts of sabatolimab as single agent were completed, and safety data suggested acceptable toxicity for subjects to begin treatment in combination. Following identification of the MTD/RP2D for the combination of sabatolimab and spartalizumab with a Q2W dosing schedule, a further dose escalation was planned to identify the MTD/RP2D with a Q4W dosing schedule. The sabatolimab in combination with decitabine treatment arm (Phase Ib) was not opened for enrollment. * Dose ranging part: During the dose ranging part various dose levels of single agent sabatolimab were tested to better understand the safety, tolerability and PK. * Phase II part (sabatolimab in combination with spartalizumab): Once the MTD and/or RP2D were declared for sabatolimab in combination with spartalizumab, additional subjects were enrolled in the Phase II part in the selected indications (melanoma and non-small cell lung carcinoma) in order to assess the preliminary anti-tumor activity. The Phase II single agent sabatolimab treatment arm was not opened for enrollment.

Conditions

• Advanced Malignancies

Interventions

Type	Name	Description
DRUG	MBG453	Anti human TIM-3 monoclonal antibody. MBG453 administered via intravenous (i.v.) infusion either every 2 weeks (Q2W) or every 4 weeks (Q4W).
DRUG	PDR001	Anti-human PD-1 monoclonal antibody. PDR001 administered via intravenous (i.v.) infusion either every 2 weeks (Q2W) or every 4 weeks (Q4W).
DRUG	Decitabine	commercially available chemotherapy

Timeline

• Start date: 2015-11-23
• Primary completion: 2022-08-30
• Completion: 2022-08-30
• First posted: 2015-11-18
• Last updated: 2023-12-06
• Results posted: 2023-12-06

Locations

14 sites across 9 countries: United States, Canada, Italy, Japan, Netherlands, Singapore, South Korea, Switzerland, Taiwan

Regulatory

• FDA-regulated drug study