mycosis fungoides
Results of a phase 2 trial suggest the drug APO866 is not suitable for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL).
Researchers said APO866 had “a reasonable toxic effect,” but it was “not powerful enough,” so the trial was stopped early.
Two of the 14 patients studied achieved a partial response during the trial, but there were no complete responses, and most patients withdrew from the study early.
The researchers described these results in a letter to JAMA Dermatology. The study was initially sponsored by Apoxis SA and later by TopoTarget A/S, which is now known as Onxeo after merging with BioAlliance Pharma.
According to Onxeo, APO866 is an injectable molecule that induces apoptosis by inhibiting the biosynthesis of NAD+ from niacinamide, which is essential for the cellular metabolism, protein modification, and calcium-dependent messenger synthesis.
In the phase 2 trial, researchers tested APO866 in 14 patients with relapsed or refractory CTCL. The patients were 19 to 83 years of age, and half were female.
Eight patients had mycosis fungoides, 3 had Sézary syndrome, 1 had CD30+ anaplastic large-cell lymphoma, 1 had poikilodermic mycosis fungoides, and 1 had CD30- nonepidermotropic CTCL. One patient had stage IB disease, 2 had stage IIA, 3 had stage IIB, and 8 had stage IVA.
The patients received a continuous intravenous infusion, via pump, of APO866 at 0.126 mg/m2/h over the course of 96 hours. Patients received this treatment every 28 days for a total of 3 cycles.
Five patients completed all 3 treatment cycles and had no major protocol violations. Nine patients discontinued treatment early due to consent withdrawal (n=2), early disease progression (n=5), or adverse events (AEs, n=2).
At week 8, 1 patient had achieved a partial response to treatment, 4 patients had stable disease, 5 had progressed, and 4 patients were not evaluable because they had withdrawn from the study.
At week 16, 1 patient had a partial response (not the same patient as at week 8), 4 patients had stable disease, and 9 patients were not evaluable due to withdrawal.
There were a total of 141 AEs, and 77 of these were considered related to APO866. Most patients (n=12) had mild to moderate AEs, but there were 7 serious AEs thought to be treatment-related. These included pyrexia, lymphopenia (n=2), spondylitis, Staphylococcal sepsis, rhabdomyolysis, and thrombocytopenia.
There were 4 deaths, but they were not considered drug-related.
The researchers said these results suggest APO866 should not be pursued as a treatment for CTCL. However, as the drug induces immunosuppression and has insulin-mimicking effects, it might prove useful for treating other conditions.
