nal-IRI

nal-IRI, also known as MM-398, is a nanoliposomal encapsulation of the chemotherapeutic irinotecan. It was developed for treating metastatic pancreatic cancer in patients previously treated with gemcitabine-based therapy. The drug works by inhibiting topoisomerase I, an essential enzyme involved in DNA transcription and replication, which promotes cell death[5]. In the Phase 3 NAPOLI-1 trial, MM-398 in combination with 5-fluorouracil (5-FU) and leucovorin achieved an overall survival of 6.1 months, a 1.9-month improvement over the 4.2-month survival demonstrated by the control arm (5-FU and leucovorin alone) in patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. The primary log-rank analysis of overall survival was statistically significant (p=0.012) with a corresponding hazard ratio of 0.67[5]. A statistically significant advantage for progression-free survival was also observed in the combination arm[5]. However, the NAPOLI trial showed that single-agent MM-398 was not superior to 5-FU and leucovorin, indicating it's not effective as a monotherapy for second-line pancreatic cancer but should be combined with 5-FU[10]. The most common Grade 3 or higher adverse events in the combination arm were neutropenia (14.5%), fatigue (13.7%), diarrhea (12.8%), and vomiting (11.1%)[5]. Gastrointestinal toxicity, particularly diarrhea, and myelosuppression (neutropenia, thrombocytopenia) are notable concerns[10].

Other names

nanoliposomal irinotecan