Efficacy and safety of lucitanib plus nivolumab in patients with advanced gynecologic malignancies: Phase 2 results from the LIO-1 study (NCT04042116; ENGOT-GYN3/AGO/LIO).

5517 Background: LIO-1 is assessing the oral antiangiogenic, multikinase inhibitor lucitanib in combination with the programmed cell death receptor 1 (PD-1) inhibitor nivolumab. Individualized lucitanib dose titration is being explored to maximize lucitanib exposure and potential clinical benefit of the combination. Here, we present data from stage 1 of a Simon 2-stage design across 4 different types of advanced gynecologic cancers from the phase 2 part of LIO-1. Methods: Patients (pts) with advanced, recurrent, or metastatic endometrial cancer (EC, who received ≥1 prior platinum-based chemotherapy); cervical cancer (CC, who received ≥1 prior platinum-based chemotherapy ± bevacizumab); high-grade ovarian cancer (OC, who received ≥2 prior chemotherapies); or EC/OC with clear-cell histology (EOCC, who received ≥1 prior platinum-based chemotherapy + taxane) were enrolled. Prior PD-1 or programmed cell death ligand 1 (PD-L1) inhibitor treatment was excluded, except for up to 10 pts in the EC cohort. Pts received lucitanib at a starting dose of 6 mg once daily (QD), escalating to 8 mg QD and then 10 mg QD if safety-based titration criteria were met, plus intravenous nivolumab 480 mg every 28 days. The data cutoff was Jan 10, 2022. Results: Across cohorts, 100 pts were enrolled to stage 1; 27 (27%) remain on treatment. To date, 28 (28%) have escalated to lucitanib 8 mg, and 17 (17%) have escalated to the maximum dose of 10 mg. Confirmed responses per RECIST v1.1 have been reported in 5/22 (22.7%; 5 partial responses [PRs]) EC pts, 7/22 (31.8%; 2 complete responses [CRs], 5 PRs) CC pts, 4/33 (12.1%; 4 PRs) OC pts, and 5/23 (21.7%; 1 CR, 4 PRs) EOCC pts. Response duration ranges from 1.9+ to 13.1+ months. Of 5 pts with EC who received prior PD-1 inhibitor, there were 2 PRs, and 1 pt with ongoing stable disease of 7+ months. Grade ≥3 treatment-emergent adverse events (TEAEs) considered related to study treatment were reported in 43 (43%) pts, with hypertension the most frequent (n = 25 [25%]). Forty-six (46%) pts had a lucitanib-related TEAE that led to lucitanib interruption and 12 (12%) had one that led to lucitanib dose reduction. Eleven (11%) and 8 (8%) pts discontinued lucitanib and nivolumab, respectively, due to a treatment-related TEAE. Safety results were generally consistent across tumor cohorts. Conclusions: The combination of lucitanib + nivolumab is active in the treatment of advanced gynecological malignancies and has a manageable safety profile through effective dose titration. Stage 2 enrollment has continued in the CC cohort. Biomarker analysis is ongoing, and more mature efficacy and safety data will be presented at the meeting. Clinical trial information: NCT04042116.