P1/2, N=160, Recruiting, Sellas Life Sciences Group | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
5 months ago
Trial completion date • Trial primary completion date • Combination therapy
Through rapid 'on-off' CDK9 inhibition, GFH009 exerts a proapoptotic effect on HHM preclinical models triggered by dynamic deprivation of crucial cell survival signals. Our results mechanistically establish CDK9 as a targetable vulnerability in assorted HHMs and, along with the previously shown superior class kinome selectivity of GFH009 vs other CDK9 inhibitors, strongly support the rationale for currently ongoing clinical studies with this agent in acute myeloid leukemia and other HHMs.
GFH009 as monotherapy is well tolerated at the tested doses and has shown clinical activity in patients with r/r lymphoma. The dose escalation in patients with AML and lymphoma is ongoing. Different dosing regimens are currently being explored for potentially better inhibition on the target.
The reference compound enitociclib (BAY 1251152) was used for experimental validation. Although several cytotoxic molecules that inhibit CDK9 are in the therapeutic pipeline, many show cross-reactivity to other CDK family members, leading to toxicity and tolerability issues. GFH009 is a potent and highly selective CDK9 inhibitor with the ability to reduce expression of downstream oncogenes required for rapid cellular division and protein expression through specific, short-lived inhibition of CDK9. We postulate that this mechanism drives GFH009's inhibition of cellular division, as tumor stabilization and shrinkage appear to be dose-dependent.
The PK profiles of GFH009 were comparable following single IV administration of two formulations of GFH009 maleate injection in SD rats, which supported application of the pH 6.0 formulation in Phase I trials in patients with relapsed/refractory hematologic conditions, including AML and lymphoma.
The PK profi les of GFH009 were comparable following single IV administration of two formulations of GFH009 maleate injection in SD rats, which supported application of the pH 6.0 formulation in Phase I trials in patients with relapsed/refractory hematologic conditions, including AML and lymphoma.