A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients With Advanced Solid Tumors

Am J Clin Oncol. 2020 Jul;43(7):484-490. doi: 10.1097/COC.0000000000000691.


Objectives: SLC-0111 is an ureido-substituted benzenesulfonamide small molecule inhibitor of carbonic anhydrase IX. The objectives of this first-in-human Phase 1 study were to determine the safety and tolerability of SLC-0111 in patients with advanced solid tumors and to establish the recommended Phase 2 dose for future clinical investigations.

Materials and methods: Using a 3+3 design, dose escalation started at 500 mg oral daily dosing of SLC-0111 in cohort 1 and increased to 1000 and 2000 mg in cohorts 2 and 3. Drug-related adverse events (AEs) were monitored to determine safety and tolerability. Pharmacokinetic analyses assessed plasma concentrations of single and repeated doses of SLC-0111. RECIST 1.1 criteria were used to assess disease progression.

Results: No dose-limiting toxicities were reported and patients dosed at ≤1000 mg exhibited fewer drug-related AEs ≥ grade 3 and fewer AEs such as nausea and vomiting, compared with the 2000-mg cohort. Forty-one percent of patients experienced dose interruptions or discontinuation and the majority (71%) of these occurred in the 2000-mg cohort. Mean Cmax and AUC(0-24) values for single doses were similar at the 1000-mg and 2000-mg dose levels. Mean Tmax and T1/2 values of SLC-0111 were similar after single and repeated dosing. Power-law analysis of Cmax and AUC0-24 showed that exposure to SLC-0111 was generally dose proportional. No objective responses were observed, but stable disease >24 weeks was observed in 2 patients.

Conclusions: SLC-0111 was safe in patients with previously treated, advanced solid tumors. The safety and pharmacokinetic data support 1000 mg/d as the recommended phase 2 dose for SLC-0111.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm
  • Antineoplastic Agents / therapeutic use*
  • Carbonic Anhydrase IX / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Phenylurea Compounds / therapeutic use*
  • Sulfonamides / therapeutic use*


  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Phenylurea Compounds
  • SLC-0111
  • Sulfonamides
  • CA9 protein, human
  • Carbonic Anhydrase IX

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