Phase 2 Placebo-Controlled Study to Assess the Efficacy/Safety of Farletuzumab plus Chemotherapy in Women with Low CA-125 Platinum-Sensitive Ovarian Cancer

Results of a placebo-controlled, phase 2 study (MORAb-003-011/ENGOT-ov27) indicate that the addition of farletuzumab to platinum-based chemotherapy was not superior to placebo/chemotherapy in improving progression-free survival or other efficacy parameters in patients with platinum-sensitive recurrent ovarian cancer in first relapse who had low alemtuzumab CA-125 levels.

Based on evidence that low CA-125 levels (≤3 × upper limit of normal [ULN]) might be associated with superior efficacy outcomes, the randomized, double-blind, placebo-controlled, phase 2 study (MORAb-003-011/ENGOT-ov27) compared the efficacy and safety of the antifolate receptor-α monoclonal antibody farletuzumab with placebo in combination with platinum-based chemotherapy, in women with low CA-125 platinum-sensitive ovarian cancer. The results of the trial were reported at the 2021 Society of Gynecologic Oncology Annual Meeting.

The study enrolled women aged ≥18 years; with CA-125 ≤3 × ULN (105 U/mL); and high-grade serous epithelial ovarian cancer; previous treatment with debulking surgery and first-line platinum-based chemotherapy (carboplatin/paclitaxel or carboplatin/pegylated liposomal doxorubicin); in first relapse (platinum-free interval, 6-36 months). During the combination treatment phase, eligible patients were randomized (2:1) to receive 6 cycles with chemotherapy every 3 weeks in combination with either farletuzumab (5 mg/kg weekly) or placebo; tumor assessments were done every 6 weeks. In the maintenance phase, therapy with farletuzumab (5 mg/kg weekly) or placebo was administered until disease progression, and tumor assessments were done every 9 weeks. The study was designed to detect a progression-free survival (PFS) hazard ratio (HR) of 0.667 (33.3% risk reduction) with farletuzumab compared with placebo, and had approximately 85% power and a 1-sided type I error rate of 0.10.

A total of 214 patients were enrolled in the study; of these, 142 patients were randomized to the farletuzumab/chemotherapy group, and 72 patients to the placebo/chemotherapy group. In the intent-to-treat population, no significant difference was noted in median PFS between the farletuzumab/chemotherapy and placebo/chemotherapy treatment groups (11.7 months vs 10.8 months; HR, 0.89). An interim analysis of overall survival showed no significant difference between treatment groups. The overall response rate was also similar between the 2 treatment groups (69.6% vs 73.5%; P = .53). No significant between-group differences were observed for any other efficacy parameters.

Safety analysis showed that serious adverse events were generally similar between the 2 treatment groups (30% with farletuzumab vs 24% with placebo plus chemotherapy). However, a higher incidence of interstitial lung disease was reported in the farletuzumab/chemotherapy combination group (7/141 [5%] vs 0/70 [0%]); among the interstitial lung events, 1 was of grade 1 severity; 4 were grade 2; and 2 were grade 3.

Based on these results, the investigators concluded that the addition of farletuzumab to chemotherapy was not superior to placebo/chemotherapy in improving PFS or other efficacy parameters in patients with platinum-sensitive recurrent ovarian cancer in first relapse who also had low CA-125 levels.

Source: Herzog T, Pignata S, Ghamande S, et al. A randomized, double-blind, placebo-controlled, phase II study to assess the efficacy/safety of farletuzumab in combination with carboplatin plus paclitaxel or carboplatin plus pegylated liposomal doxorubicin (PLD) in women with low CA-125 platinum-sensitive ovarian cancer. Gynecol Oncol. 2021;162(suppl_1):S38-S39.