SELLAS Life Sciences’ Phase 2 trial of SLS009 (tambiciclib), a CDK9 inhibitor, for relapsed/refractory acute myeloid leukemia (r/r AML) has met all primary endpoints. The trial demonstrated a 44% overall response rate (ORR) in patients with AML with myelodysplasia-related changes (AML MR) at the optimal dose and a median overall survival (mOS) of 8.9 months, significantly exceeding the historical benchmark of 2.4 months. Based on these positive results, the FDA recommended advancing SLS009 to a randomized trial including newly diagnosed AML patients, potentially supporting a future New Drug Application (NDA).
This success holds substantial promise for AML patients, particularly those with relapsed/refractory disease who often face limited and ineffective treatment options. The high response rates observed in the Phase 2 trial, especially among high-risk subtypes like AML MR and ASXL1-mutated AML, suggest that SLS009 could offer a much-needed new therapeutic approach. The improved survival data, coupled with a favorable safety profile, further strengthens the potential of SLS009 to change the treatment landscape for this challenging disease.
The Phase 2 trial enrolled 54 evaluable r/r AML patients. The ORR was 33% across all cohorts and dose levels and 40% for the 30mg twice-weekly dose. Among AML MR patients at this optimal dose, the ORR was 44%, reaching 50% in both ASXL1-mutated AML MR and M4/M5 subtypes. The mOS for AML MR patients was 8.9 months, and for those with a median of one prior line of therapy, it was 8.8 months, far surpassing the historical benchmark. Notably, SLS009 in combination with venetoclax/azacitidine was well-tolerated without dose-limiting toxicities. The upcoming randomized trial will focus on newly diagnosed AML patients, including those unlikely to benefit from standard venetoclax/azacitidine therapy and those showing early resistance. This strategic approach aims to maximize clinical benefit by intervening earlier in the disease course.
The positive Phase 2 results and the FDA’s recommendation pave the way for SLS009’s advancement into a pivotal trial involving newly diagnosed AML patients. This positions SLS009 to potentially become a first-line treatment option, offering hope for improved outcomes in a broader population of AML patients. The upcoming trial’s focus on precision medicine, incorporating molecular profiling and early resistance identification, could further enhance SLS009’s therapeutic impact. This sets the stage for a significant shift in the AML treatment paradigm, potentially offering a more effective and tolerable option for patients who currently face a dismal prognosis.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
