NEW YORK – Drug developer Humanigen on Tuesday said that the first chronic myelomonocytic leukemia patient has received treatment in the PREACH-M trial of its investigational GM-CSF neutralizing antibody lenzilumab.
The multi-cohort PREACH-M trial will enroll 72 CMML patients at five sites in Australia. Patients will have specific mutations driving their disease.
In one cohort, CMML patients with RAS pathway mutations in genes such as KRAS, NRAS, or CBL — considered to have aggressive disease — will receive lenzilumab and high-dose azacitidine. Those with a TET2 mutation will receive high-dose sodium ascorbate and azacitidine in another arm. Patients with both RAS pathway and TET2 mutations, who meet other inclusion and exclusion criteria, will receive lenzilumab in a third arm. Patients who lack any mutations will be considered "screening failures," according to the company, but will still receive free gene sequencing, which is currently not funded by Australia's healthcare system.
The PREACH-M trial is sponsored by the South Australian Health and Medical Research Institute and is supported by a National Health and Medical Research Council grant to the University of Adelaide. Burlingame, California-based Humanigen is providing lenzilumab for this study through its Australian subsidiary Humanigen Australia.
Researchers designed the PREACH-M trial based on preclinical and early clinical studies suggesting that CMML patients with RAS pathway mutations would benefit from lenzilumab. In one Phase I trial, a third of 15 CMML patients benefited from lenzilumab, and those with NRAS mutations appeared to benefit more.
Since CMML is a rare disease, occurring in 0.3 per 100,000 Australians, the company estimated it may take three years to reach the target enrollment in the trial. Researchers will track patients' complete response and partial response to a year of treatment in the various arms. They will also assess overall and progression-free survival two years after the start of treatment.
Currently, median survival for CMML patients is around 30 months, and for more than three decades there hasn't been much progress made in improving patients' outcomes. “The overarching goal of the clinical trial is to improve response rates and survival," Daniel Thomas, the coordinating investigator for the trial and associate professor of hematology at the University of Adelaide, said in a statement. "If we can improve response rates to 30 percent [or] 50 percent, from the current 18 percent response rate normally seen in CMML patients treated with azacitidine, we think median survival may be increased to more than three years."