A Phase I/Ib study of folate immune (EC90 vaccine administered with GPI-0100 adjuvant followed by EC17) with interferon-α and interleukin-2 in patients with renal cell carcinoma.
Folate immune (EC90 vaccine with GPI-0100 adjuvant followed by EC17) is a novel folate-targeted hapten immunotherapy designed to exploit the overexpression of folate receptors on renal cell carcinoma (RCC) cells. In this open-label, phase I/II clinical study, we report the safety, pharmacokinetics, and antitumor activity of folate immune with concurrent interleukin-2 (IL-2) and interferon-α (IFN-α) in patients with recurrent or metastatic RCC. Twenty-four patients were enrolled. Following 2 phase I cohorts of 6 patients each, we extended the study to 12 additional patients: 18 received weekly vaccination of 1.2 mg of EC90 with 3.0 mg of GPI-0100 adjuvant for 4 weeks. Beginning on cycle 1, day 8, 0.3 mg/kg of EC17 was administered once daily, 5 days per week (Monday-Friday) for 4 consecutive weeks. Beginning on cycle 1, day 15, IL-2 and IFN-α were administered at doses of 12 and 3.0 MIU, respectively, after the EC17 dose, 3 times per week (Monday, Wednesday, and Friday) for 3 weeks. In cycle 2, IL-2 and IFN-α, doses of 7.0 and 3.0 MIU, respectively, were administered 3 days per week (Monday, Wednesday, and Friday) for 4 consecutive weeks. No dose-limiting toxicities were observed. Most adverse events reported were grade 1 or 2, with only twelve grade ≥3 toxicities reported. Sixteen patients had progressive disease, 7 patients were observed to have stable disease, and 1 patient achieved a partial response lasting 71 days. Overall, folate immune plus low-dose IFN-α and IL-2 was safe and well tolerated with some observed clinical activity.
*Department of Internal Medicine, Division of Oncology, University of Texas Health Science Center at Houston (Medical School) †Memorial Hermann Cancer Center ‡Medical School, University of Texas Health Science Center at Houston, Houston, TX §Endocyte Inc. ∥Department of Chemistry, Purdue University, West Lafayette, IN.
Robert J
RJ
Amato
Aditya
A
Shetty
Yingjuan
Y
Lu
P Ron
PR
Ellis
Virginia
V
Mohlere
Natalie
N
Carnahan
Philip S
PS
Low
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D019793:Fluorescein; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006241:Haptens / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016896:Treatment Outcome
D019496:Cancer Vaccines; D006241:Haptens; D016898:Interferon-alpha; D007376:Interleukin-2; D005492:Folic Acid; D019793:Fluorescein