Avutometinib: lymph node follicular hyperplasia, plasma cells and inflammatory infiltrates in rats and monkeys
“Histopathology findings of hyperplasia of the lymph follicle, increased plasma cells of the medulla, and inflammatory cell infiltrates in the sinus of the lymph nodes were noted in both species.”
✓ VerifiedFDA multi-discipline review, p. 36Source ↗
Biodistribution & persistence
Defactinib: distributes to pigmented skin and uveal tract, suggesting melanin affinity
“radioactivity was reported in the pigmented tissues (pigmented skin, eye [uveal tract, lens]), indicating a possible affinity of defactinib to melanin.”
✓ VerifiedFDA multi-discipline review, p. 39Source ↗
Modality-specific risk
GI, skin, ocular, renal, hematologic and hepatic toxicities, all also seen clinically
“Consistent with nonclinical findings, gastrointestinal, skin, ocular, renal, hematologic, and clinical chemistry (elevations in liver enzymes) toxicities have occurred clinically.”
✓ VerifiedFDA multi-discipline review, p. 40Source ↗