The phase 3 ASC4FIRST trial (NCT04971226) compared the BCR-ABL1 TKI inhibitor asciminib to investigator-selected standard-of-care TKIs in 405 participants with previously untreated CML in the chronic phase. Participants were randomised 1:1 to asciminib or standard of care TKIs and treatment with the first-generation TKI imatinib, or one of the second-generation TKIs bosutinib, dasatinib, or nilotinib was permitted for ≤2 weeks before randomisation.
Prof. Andreas Hochhaus (Jena University Hospital, Germany) presented the results and noted that randomisation was stratified by pre-randomisation TKI selection and by the European Long-Term Survival (ELTS) risk category. The primary endpoints were major molecular response (MMR) at week 48 and MMR within the imatinib stratum1.
The first primary endpoint was met, with 67.7 and 49.0 % of the participants in the asciminib arm and control arm reaching an MMR at week 48 (Δ 18.9; 95 % CI 9.6–28.8; P<0.001). In addition, MR4.5 (BCR::ABL1 ≤0.0032 %) was seen in 16.9 % of participants in the asciminib arm compared to 8.8 % in the control arm. In the imatinib stratum, the MMR rates were 69.3 % and 40.2 %, in favour of the asciminib arm, meeting the second primary endpoint (Δ 29.6; 95 % CI 16.9–42.2; P<0.001). Of note, the difference in MMR between the asciminib arm and control arm within the second-generation TKI stratum was less pronounced, with 8.8 % (95 % CI -5.1 to 21.5).
Fewer grade ≥3 adverse events were documented in the asciminib arm (38.0 %) compared to participants who received imatinib (44.4 %) or second-generation TKIs (54.9 %). Similarly, the adverse events-related treatment discontinuation rate was lower (4.5 vs 11.1 and 9.8 %) on asciminib. “We saw less neutropenia, anaemia, and lymphopenia with asciminib,” added Prof. Hochhaus. Also, diarrhoea, nausea, and muscle spasms were less common in the asciminib arm.
Asciminib displayed a favourable safety profile and provided better efficacy outcomes than first-line standard of care TKIs in newly diagnosed participants with CML in the chronic phase.
Medical writing support was provided by Robert van den Heuvel.