vodobatinib (SCO - 088)

Vodobatinib demonstrates a favorable preclinical absorption, distribution, metabolism, and excretion profile, with high metabolic stability, minimal efflux liability, and selective tissue distribution. These findings support its continued clinical development in chronic myeloid leukemia and potentially other Bcr-Abl 1 driven malignancies.

P1/2, N=124, Terminated, Sun Pharma Advanced Research Company Limited | Active, not recruiting --> Terminated; Closed for administrative, non-safety-related reasons.

P=N/A, N=0, Temporarily Not Available, Sun Pharma Advanced Research Company Limited

For intravenous dosing, AUC0-∞ was 9475 ng·h/mL (DBS) versus 10,109 ng·h/mL (plasma), and for oral dosing, Cmax values were 568 ng/mL (DBS) versus 544 ng/mL (plasma). Oral bioavailability was nearly identical between matrices (98.7% for DBS vs. 97.9% for plasma), confirming the reliability of DBS sampling for PK studies of vodobatinib.

Pooled analysis of the phase 1 and 2 studies showed clinically meaningful antileukaemic activity of vodobatinib and a tolerable safety profile in patients with advanced chronic myeloid leukaemia who previously received multiple TKIs, including ponatinib and asciminib, addressing an otherwise unmet clinical need. The phase 2 study was statistically underpowered and warrants further investigation in a phase 3, randomised controlled trial and in an earlier treatment setting of the disease.

Overall, our findings unveil an additional pharmacological facet of vodobatinib against ABCB1 and ABCG2 activity, suggesting its potential incorporation into combination therapy for a specific subset of patients with tumors characterized by high ABCB1 or ABCG2 levels. Further investigation is warranted to fully elucidate the clinical implications of this therapeutic approach.

P1/2, N=122, Active, not recruiting, Sun Pharma Advanced Research Company Limited | Recruiting --> Active, not recruiting | N=303 --> 122 | Trial primary completion date: Jan 2026 --> Aug 2026

Recently approved by FDA, the first-of-its-kind STAMP inhibitor asciminib has proven safe and effective, obtaining deep and stable molecular responses even in heavily pretreated patients and with T315I mutation...Among these, novel agents such as vodobatinib and olverembatinib have provided promising result in clinical trials, representing valuable therapeutic possibilities in intolerant or refractory patients. Therefore, a more complex therapeutic paradigm is expected in the near future.

P1/2, N=303, Recruiting, Sun Pharma Advanced Research Company Limited | Trial primary completion date: Aug 2022 --> Jan 2026

Vodobatinib continues to be associated with favourable long term safety and efficacy in heavily pre-treated CML failing ≥ 3 prior TKIs, including ponatinib. Phase 2 study evaluating vodobatinib in pts failing at least 3 prior lines of therapy, including ponatinib, is ongoing.