sabatolimab (MBG453)

Aside from allogeneic transplantation, the current standard of care approach for higher-risk myelodysplastic syndromes/neoplasms (HR-MDS) remains monotherapy with a hypomethylating agent (HMA) including azacitidine, decitabine, or oral decitabine/cedazuridine...In this review, we discuss lessons learned from the recently reported negative trials of azacitidine in combination with eprenetapopt (APR-246), magrolimab, pevonedistat, sabatolimab, tamibarotene, and venetoclax...Instead, we advocate for using the IWG 2023 response criteria to better capture clinically meaningful benefits in HR-MDS. Lastly, we emphasize the need for the scientific community to access patient-level data and samples from failed phase 3 trials in an efficient and expedited fashion to inform the development of subsequent trials.

P2, N=20, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Nov 2026 | Trial primary completion date: Jun 2024 --> Nov 2024

P1, N=16, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2025 --> Sep 2026

Functional assays demonstrated that TIM3 blockade with sabatolimab restored T cell cytotoxicity, leading to enhanced leukemia cell apoptosis in ER patients. These findings highlight TIM3 as a critical regulator of T cell exhaustion and immune suppression in patients with ER and provide a rationale for the therapeutic use of TIM3 blockade in preventing and treating relapses after allo-HSCT.

P1/2, N=45, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Sponsor Decision

P2, N=39, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Lack of efficacy in the program as demonstrated in the earlier CMBG453B12301 (STIMULUS MDS-2) study.

P1/2, N=24, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Study was stopped following a strategic decision from the Sponsor. It was not based on any safety findings or safety concerns with sabatolimab.

Forty-four patients were enrolled in Part 1 of the study of ruxolitinib in combination with siremadlin, rineterkib, sabatolimab, crizanlizumab, or NIS793. Overall, available data from ADORE suggest the feasibility and benefits of combining novel agents with ruxolitinib in patients with suboptimal response to ruxolitinib alone. This trial was registered at www.clinicaltrials.gov as #NCT04097821.

P2, N=90, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; The study was terminated because results from 2 trials in the program were negative (including the main trial) and Novartis decided to terminate the program all together.

P2, N=127, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; In December 2023, Novartis decided to terminate the sabatolimab clinical development program early after Phase II and III studies failed to meet their primary objectives. The termination was not due to safety concerns.

P2, N=20, Completed, Novartis Pharmaceuticals | Terminated --> Completed

P3, N=530, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Despite positive trends identified post unblinding after Overall Survival primary analysis, the study did not show statistical significance in its primary endpoint, overall survival. No new safety findings were detected.