Onivyde for the therapy of multiple solid tumors

Figures & data

Figure 1 Chemical structure of irinotecan (A). Schematic structure of Onivyde: the basic molecule irinotecan forms a nanoscale complex with either poly(phosphate) or sucrose octasulfate in the liposome interior (B).

Table 1 Pharmacokinetic variables for free and nanoliposomal CPT-11 in rats

Pharmacokinetic variables	Free CPT-11	Nanoliposomal CPT-11
t1/2 (hours)	0.27	6.80
AUC∞ (µg·h/mL)	6.2	1,407.8
CL (mL/h)	1,609	7.10
Vd (mL)	616.4	69.7
MRT (hours)	0.4	9.8
t1/2 of CPT-11 release (hours)	–	14.0

Abbreviations: t_1/2, terminal half-life; AUC_∞, area under the concentration vs time curve in plasma based on the sum of exponential terms; CL, clearance calculated from exponential terms; V_d, volume of distribution; MRT, mean residence time calculated from exponential terms.

Table 2 Characteristics of the clinical trials of Onivyde for the treatment of multiple solid tumors

Study	Trial	Design	Tumor type	Outcomes
Chang et al^Citation22	Phase I	Dose escalation	Advanced solid tumors	MTD: 120 mg/m^2 monotherapy at 3-week interval
Roy et al^Citation18	Phase II	Randomized, three-arm	Esophago-gastric cancer	ORR: 13.6% (Onivyde) vs 6.8% (irinotecan) vs 15.9% (docetaxel)
Chibaudel et al^Citation19	Phase II	Randomized, noncomparative	Colorectal cancer	ORR: 16.7% (Onivyde + 5-FU/LV) vs 11.5% (irinotecan + 5-FU/LV)
Ko et al^Citation20	Phase II	Multicenter, open-label, single arm	Pancreatic cancer	mOS: 5.2 months; mPFS: 2.4 months
Von Hoff et al^Citation21	Phase III	Randomized, open-label	Pancreatic cancer	mOS: 6.1 (Onivyde + 5-FU/LV) vs 4.2 (5-FU/LV) months mPFS: 3.1 (Onivyde + 5-FU/LV) vs 1.5 (5-FU/LV) months

Abbreviations: MTD, maximum tolerated dose; ORR, objective response rate; 5-FU/LV, 5-fluorouracil/leucovorin; mOS, median overall survival; mPFS, median progression-free survival.

ChangTCShiahHSYangCHPhase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patientsCancer Chemother Pharmacol201575357958625577133

 PubMed Web of Science ®Google Scholar

RoyACParkSRCunninghamDA randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinomaAnn Oncol20132461567157323406728

 PubMed Web of Science ®Google Scholar

ChibaudelBMaindrault-GoebelFAndréTPEPCOL: a randomized noncomparative phase II study of PEP02 (MM-398) or irinotecan in combination with leucovorin and 5-fluorouracil as second-line therapy in patients with unresectable metastatic colorectal cancer – a GERCOR StudyJ Clin Oncol201533Suppl 3 Abstr 751

 Web of Science ®Google Scholar

KoAHTemperoMAShanYSA multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancerBr J Cancer2013109492092523880820

 PubMed Web of Science ®Google Scholar

Von HoffDLiCPWang-GillamANapoli-1: randomized phase 3 study MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer progressed on or following gemcitabine-based therapyAnn Oncol201425Suppl 2ii105ii106

 Google Scholar