METHODS: We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS).
RESULTS: At study termination with a median follow-up of 15.2 months (range 1.2-28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3-16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event.
CONCLUSIONS: TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222, https://clinicaltrials.gov/search?term=NCT02978222.
方法:我们进行了随机,双盲,多中心,II期研究旨在评估TPIV200(一种与GM-CSF混合的多表位FRα肽疫苗)与单独GM-CSF的安全性和有效性,这些女性在至少4个周期的一线铂类治疗后没有疾病进展。患者每4周一次皮内接种疫苗,最多6次,随后是12周间隔的6次疫苗接种的加强期。主要终点包括安全性,耐受性,无进展生存期(PFS)。
结果:在研究终止时,中位随访时间为15.2个月(范围1.2-28.4个月),119例意向治疗患者中有68例出现疾病进展(TPIV200+GM-CSF组55%,单独GM-CSF组59%)。中位PFS为11.1个月(95%CI8.3-16.6个月),治疗组之间无显着差异(TPIV200GM-CSF为10.9个月,GM-CSF为11.1个月,HR,0.85;上限90%CI1.17]。无患者经历≥3级药物相关不良事件。
结论:TPIV200耐受性良好,但与PFS改善无关。需要额外的研究来揭示使用靶向FRa的多表位疫苗的潜在协同作用。试用注册NLM/NCBI注册中心,NCT02978222,https://clinicaltrials.gov/search?term=NCT02978222.