Modra Pharmaceuticals’ oral docetaxel has performed comparably to the intravenous incumbent in a phase 2b clinical trial, emboldening the company to start work on a pivotal study.
Docetaxel is given intravenously because of its low bioavailability. Researchers have proposed a range of ways to overcome barriers to oral delivery, such as the use of nanocarriers. Modra’s solution is to give docetaxel with ritonavir, the protease inhibitor Pfizer uses in Paxlovid to slow the breakdown of its oral COVID-19 antiviral.
To test whether the boosting agent enables oral delivery of docetaxel, Modra randomized 102 patients with metastatic castration-resistant prostate cancer to receive either one of two bi-daily weekly doses of its oral candidate, ModraDoc006/r, or intravenous docetaxel.
The overall response rate in the ModraDoc006/r arm was 44%, compared to 39% in the control arm. Prostate-specific antigen responses were similar, too, coming in at 50% in the oral arm and 57% in the intravenous cohort.
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There was more divergence between the arms in the safety and tolerability data. Patients with low levels of the white blood cell neutrophils were rarer in the ModraDoc006/r arm. Modra said neutropenia was “eliminated” at the lower dose of ModraDoc006/r and reduced at the higher dose, affecting 14% of patients versus 25% in the intravenous cohort. Nerve damage and hair loss were reduced at the lower dose, according to Modra.
“Advanced prostate cancer patients frequently do not receive the benefits of IV docetaxel chemotherapy due to advanced age [and] comorbidities. An oral chemo that is easier to tolerate—with less risk of cytopenias, hair loss and neuropathy—would make the benefits of chemo accessible to the majority of patients with metastatic prostate cancer,” Ulka Vaishampayan, M.D., the principal investigator and a University of Michigan professor, said in a statement.
Gastrointestinal toxicities were “slightly” more frequent in both ModraDoc006/r arms versus the intravenous cohort. Modra said the gastrointestinal adverse events were “predominantly mild.”