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. 2016 May 27;7(32):52553–52574. doi: 10.18632/oncotarget.9651

Table 1. Key clinical trials of FRα-drug conjugate therapeutics.

Drug Name Alternative Name(s) Tumor Type Trial Design Efficacy Outcome Safety Outcome Imaging Outcome Reference/Trial Number
Vintafolide

  1. EC145

  2. Folate-conjugated DAVLBH

 Platinum-resistant ovarian cancer Randomized phase II trial of Vintafolide + PLD vs. PLD alone in platinum-resistant ovarian cancer (PRECEDENT) Vintafolide demonstrated significantly improved clinical activity compared with PLD alone. Median PFS was 5.0 and 2.7 months for vintafolide + PLD and PLD-alone arms, respectively (P = 0 .031). Greatest benefit observed in patients with 100% FR+ lesions, with median PFS 5.5 vs. 1.5 months for PLD alone (P = 0.013) Vintafolide + PLD was well tolerated. Frequency of leukopenia, neutropenia, abdominal pain, and peripheral sensory neuropathy was higher in vintafolide + PLD vs. PLD arm N/A [77] NCT00722592
FR+ platinum-resistant ovarian cancer Phase III study of vintafolide + PLD vs. PLD alone in patients with FR+ platinum-resistant ovarian cancer (PROCEED). At a prespecified interim data analysis, cessation of the study was recommended because vintafolide + PLD vs. PLD alone did not meet the prespecified criteria for PFS No safety concerns were detailed N/A [28] NCT01170650
FR+ NSCLC Randomized, open-label, phase II trial of vintafolide as second-line treatment vs. vintafolide + docetaxel vs. docetaxel alone in patients with FR+ NSCLC (TARGET) Preliminary data for vintafolide + docetaxel showed improvement across all efficacy endpoints vs. docetaxel alone. The best improvement was observed in the predefined adenocarcinoma patient subgroup The safety profile was manageable and consistent with the AEs observed with both therapies N/A [75, 76] NCT01577654
EC0225

  1. Folate–desacetylvinblastine-hydrazide

  2. folate–mitomycin C

 Solid tumors Phase I study of EC0225 in patients with solid tumors (refractory or metastatic) Disease stabilization (≥ 4 months) was observed in 26/63 patients EC0225 was well -tolerated at doses ≤2.3 mg/m2. Most frequent AEs included anemia, constipation, leukopenia, fatigue. G3 hypotension and G4 neutropenia occurred in 1 patient each at the highest dose tested (2.88mg/m2) defining the MTD N/A [79 NCT00441870
Epofolate

  1. BMS-753493

  2. Folate-conjugated epothilone A

 Solid tumors Phase I study of epothilone folate (BMS-753493) in patients with advanced solid tumors Best overall response was SD in 19% patients. Median duration of response was 85 days. No correlation between FR status and response. Interim analysis indicated that the benefit risk profile of BMS-753493 was not favorable and did not support further investigation of this agent The MTD was reached. DLTs included ALT and AST elevations, diarrhoea, nausea, fatigue, oesophagitis and mucosal inflammation N/A [80, 81] NCT00546247
EC0489 Folate–desacetylvinblastine hydrazide with modified linker Solid tumors Phase I study of EC0489 in patients with refractory or metastatic tumors Not reported Patients treated at 2.5mg/m2 experienced toxicities characteristic of vinca alkaloids (e.g., mild neuropathy), but not significant constipation nor gastrointestinal-related toxicity N/A [82] NCT00852189
EC1456 Folate–tubulysin TNBC, advanced NSCLC and ovarian cancer Phase I dose-escalation study of EC1456 (Part A) including a study of efficacy in patients with TNBC, advanced NSCLC and ovarian cancer treated at the MTD (Part B) Data awaited Data awaited N/A NCT01999738

AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DLT, dose-limiting toxicity; G, CTCAE grade; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; SD, stable disease; TNBC, triple negative breast cancer. Clinical trial number (NCT) available from: http://clinicaltrials.gov.