Scemblix (asciminib)

P1, N=12, Not yet recruiting, Washington University School of Medicine | Trial completion date: Nov 2027 --> Mar 2028 | Initiation date: Apr 2026 --> Aug 2026 | Trial primary completion date: Oct 2027 --> Feb 2028

P1/2, N=30, Not yet recruiting, Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

P3, N=8, Terminated, Sarit Assouline | N=164 --> 8 | Trial completion date: Dec 2025 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jul 2025; Insufficient patient accrual

In patients experiencing failure of frontline therapy due to resistance or intolerance, multiple second- and third-line options are available, including second-generation TKIs, ponatinib, and asciminib, as well as novel investigational agents, including the ABL1 kinase domain inhibitors olverembatinib and ELVN-001 and the STAMP inhibitors TGRX-678 and TERN-701. In this review, we discuss the recent advances in the treatment of CML-CP and challenge some established management practices.

P1/2, N=14, Not yet recruiting, Novartis Pharma AG

P1/2, N=30, Not yet recruiting, M.D. Anderson Cancer Center

P1/2, N=7, Not yet recruiting, Novartis Pharma AG

P1/2, N=50, Not yet recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2035 --> Jun 2036 | Trial primary completion date: Jan 2033 --> Jul 2033

P=N/A, N=380, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=50, Not yet recruiting, Novartis Pharmaceuticals | Initiation date: Mar 2026 --> Jul 2026

Second-generation and third-generation TKIs further improved outcomes by targeting most imatinib-resistant mutations, with ponatinib-based regimens achieving deep molecular responses and long-term survival in most patients. Concurrently, immunotherapies like blinatumomab and CAR-T cells have enabled potent chemotherapy-free strategies, yielding high molecular response rates and challenging the necessity of allo-HSCT for all patients. Current evidence supports reserving allo-HSCT for high-risk patients, while those with sustained minimal residual disease (MRD) negativity may be cured with TKI and immunotherapy alone. Future progress hinges on optimizing combinations, integrating novel agents like asciminib and venetoclax, and leveraging MRD and genomic profiling for precision medicine.

P1/2, N=42, Not yet recruiting, Duke University | Initiation date: Feb 2026 --> Jul 2026