LIO-1: Lucitanib + nivolumab in patients with advanced solid tumors—Updated phase 1b results and initial experience in phase 2 ovarian cancer cohort.
Authors: Erika P. Hamilton, Camille Catherine Jackson, Ramez Nassef Eskander, Floor Jenniskens Backes, Vicky Makker, Fernanda Musa, Alexander Olawaiye, Jill Alldredge, Bhavana Pothuri, Angeles Alvarez Secord, Nicole Concin, Antonio Gonzalez Martin, Jowell Go, Kenton Wride, Denise M. Lepley, Teresa Cameron, Manish R. Patel
Journal: Journal of Clinical Oncology (2021)

5538 Background: The phase (Ph) 1b part of LIO-1 (NCT04042116; ENGOT-GYN3/AGO/LIO) assessed the oral antiangiogenic, multikinase inhibitor lucitanib + immune checkpoint inhibitor nivolumab, confirming the recommended Ph2 dose (RP2D) of lucitanib as 6 mg QD + nivolumab (480 mg IV every 28 days). To maximize lucitanib exposure and potential clinical benefit of the combination, individualized lucitanib dose titration is being explored in a Ph2 part, across 4 recurrent gynecologic malignancies (endometrial, cervical, ovarian, and ovarian/endometrial clear-cell cancers) using a Simon 2-stage design. We present updated Ph1b data and describe initial experience for the first 24 patients (pts) enrolled in the Ph2 ovarian cancer (OC) cohort. Methods: In Ph1b, pts with advanced, metastatic solid tumors received lucitanib at 6, 8, and 10 mg QD + nivolumab (in a 4+3 dose escalation). In the Ph2 OC cohort, pts with recurrent high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer (excluding clear-cell histology) with ≥2 prior chemotherapy regimens (including ≥1 platinum doublet) received the combination at RP2D; lucitanib dose was escalated from 6 mg to 8 mg and then to 10 mg QD for pts who met safety-based titration criteria. Visit cutoff was Feb 1, 2021. Results: In the Ph1b part (N = 17), median treatment duration was 109 days (range 14–505+). There has been 1 confirmed complete response (CR; anal cancer) and 1 confirmed partial response (PR; cervical cancer) per RECIST v1.1 with durations of 7.1 and 12.8 months, respectively. Ten pts had stable disease (SD), 3 had progressive disease, and 2 were nonevaluable; 3 pts remain on treatment. Overall disease control rate (CR + PR + SD ≥16 wk) was 47.1%. One dose-limiting toxicity (DLT; grade [G] 3 proteinuria) was observed in a pt receiving lucitanib 6 mg, leading to lucitanib discontinuation; no DLTs were seen at 8 or 10 mg. G ≥3 treatment-emergent adverse events (TEAEs) reported in ≥2 pts included hypertension (HTN; n = 4), fatigue (n = 2), and proteinuria (n = 2). Of the first 24 pts enrolled in the Ph2 OC cohort, 13 (54%) remain on treatment (median duration 59 [2–167+] days). Most frequent any-grade TEAEs were HTN (n = 10), fatigue (n = 8), nausea (n = 7), and proteinuria (n = 6). The only G ≥3 TEAE experienced in ≥2 pts was HTN (n = 4); 1 pt discontinued due to G4 HTN/G2 angina pectoris and 1 pt to G2 colonic perforation. To date, 21 pts have completed ≥1 cycle; 11 met safety-based dose-titration criteria, 10 of whom escalated to the 8 mg lucitanib dose. Of these, 5 pts subsequently escalated to 10 mg. One pt required dose reduction from 6 mg to 4 mg lucitanib. Conclusions: Ph1b data suggest that lucitanib + nivolumab has promising signs of antitumor activity. A safety-based dose-titration strategy appears feasible with manageable toxicity, based on experience from the Ph2 OC cohort to date; efficacy data from this cohort will also be presented. Clinical trial information: NCT04042116.