NEW YORK – Kronos Bio said on Thursday that it has dosed the first patient in a Phase I/II trial evaluating the activity of its CDK9 inhibitor, KB-0742, in MYC-amplified solid tumors.
Kronos is working with Tempus to sequence samples from patients enrolled in the trial using its xT broad-panel genomic assay and conduct computational analysis. The company will retrospectively sequence patients enrolled in the dose escalation portion of the study for MYC amplification and overexpression. Kronos may also use the use assay to prospectively sequence patients enrolled in the second expansion stage of the trial. Tempus will also provide Kronos access to its multimodal database to help with target enrichment and concordance studies.
The trial will enroll about 100 patients with advanced solid tumors or non-Hodgkin lymphoma. The first stage of the study will assess the safety, pharmacokinetics, and pharmacodynamics of the drug. Once the dose and schedule are determined, the study will expand to include patients with MYC-amplified solid tumors and other transcriptionally addicted cancers, like soft tissue sarcomas.
The expansion will be split into two cohorts: one comprising patients with relapsed or refractory solid tumors with evidence of MYC amplification or overexpression, and another consisting of patients with relapsed or refractory soft tissue sarcomas with evidence of transcription factor dysregulation.
The researchers will also measure the incidence of adverse events, the number patients with dose-limiting toxicity, maximum tolerated dose, and maximal plasma concentration in both stages of the trial, along with progression-free survival, disease control rate, duration of disease control, overall response rate, and duration of response.
"Scientific research has established that MYC requires CDK9 to drive its own expression and to drive expression of its target genes," Jorge DiMartino, chief medical officer and executive VP for clinical development at Kronos, said in a statement. "With KB-0742's high selectivity for CDK9 and oral bioavailability, we have a unique opportunity in this Phase I/II clinical trial to investigate an optimal dose and schedule designed to provide appropriate target engagement and acceptable safety that could allow us to leverage CDK9 inhibition as an approach to treating MYC-amplified cancers."
According to the San Mateo, California-based firm, MYC is a transcription factor that is amplified in about 30 percent of solid tumors, including lung, ovarian, esophageal, breast, stomach, pancreatic, and liver cancer.
Kronos expects to report initial safety data for KB-0742 in late 2021. The company said that initial data from the expansion cohort of patients with MYC-amplified solid tumors will read out in in 2022.