vodobatinib (SCO - 088)

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.

K0706 is a novel BCR-ABL1 TKI currently under clinical investigation with structural elements similar to those of ponatinib and dasatinib. We demonstrate that while K706 retains efficacy against a large spectrum of clinically relevant mutations, it does not appear to have activity against BCR-ABL1T315I. Early trial experience suggests excellent tolerability, which may positively impact the place of K0706 within the ever-expanding CML treatment paradigm.

Introduction: Despite availability of several BCR-ABL1 TKIs for treatment of CML, some patients (pts) fail ≥3 TKIs and/or have co-morbidities that limit use of 2nd generation TKIs (2GTKI: Nilotinib, Dasatinib and Ponatinib). K0706 has acceptable safety profile with activity in heavily pre-treated patients who had failed at least ≥3 prior lines of TKIs. The study provides early proof of principle for the effectiveness of K0706 in a setting with few available treatment options.