title: XMT-1001, a novel polymeric camptothecin pro-drug in clinical development for patients with advanced cancer.
abstract: An overview of XMT-1001 is provided in the context of other topoisomerase I inhibitors conjugated to polymers or encapsulated in liposomes. XMT-1001 is a novel polymeric pro-drug derivative of camptothecin (CPT) with a molecular weight of 70 kDa, in which CPT is chemically tethered to a hydrophilic, biodegradable polyacetal polymer, poly(1-hydroxymethylethylene hydroxymethylformal), also called PHF or Fleximer(R). XMT-1001 releases CPT via intermediates camptothecin-20-O-(N-succinimidoglycinate) (CPT-SI), and camptothecin-20-O-(N-succinamidoyl-glycinate) (CPT-SA) over an extended time period. XMT-1001 has an improved therapeutic window compared to CPT and irinotecan in human tumor xenograft models, providing a compelling rationale for clinical development. A unique feature of XMT-1001 is its dual phase release mechanism for CPT which may result in lower levels of CPT in the urine and less bladder toxicity, a serious dose limiting toxicity associated with CPT and CPT conjugated to other polymers. XMT-1001 is being evaluated in patients with advanced cancer in an ongoing Phase 1 trial.
authors.affiliation: Mersana Therapeutics, Inc., 840 Memorial Drive, Cambridge, MA 02139, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Yurkovetskiy
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fram
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D017321:Clinical Trials, Phase I as Topic; D003692:Delayed-Action Preparations; D006801:Humans; D000077146:Irinotecan; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D011108:Polymers / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D011355:Prodrugs; D059004:Topoisomerase I Inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D011108:Polymers; D011355:Prodrugs; D059004:Topoisomerase I Inhibitors; C546777:XMT 1001; C506479:poly(1-hydroxymethylethylene hydroxymethylformal); D000077146:Irinotecan; D002166:Camptothecin