Abstract P6-21-01: Xentuzumab (BI 836845), an insulin-like growth factor (IGF)-neutralizing antibody (Ab), combined with exemestane and everolimus in hormone receptor-positive (HR+) locally advanced/metastatic breast cancer (LA/mBC): Randomized phase 2 results

Background: Xentuzumab (Xen), an IGF-1/-2-neutralizing Ab, binds IGF-1 and IGF-2, inhibits their growth-promoting signaling, and suppresses AKT activation by everolimus (Ev). This Phase 1b/2 trial evaluates Xen in combination with Ev and exemestane (Ex) in HR+/HER2− LA/mBC. Methods: The two-arm, open-label, randomized Phase 2 part enrolled female patients (pts) with HR+/HER2− LA/mBC not amenable to curative therapy and refractory to nonsteroidal aromatase inhibitors. Pts were randomized (1:1) to: oral Ev (10 mg/d) + Ex (25 mg/d); or Xen (1000 mg/wk iv) + Ev (10 mg/d) + Ex (25 mg/d). Randomization was stratified by visceral metastases (VM; Y vs N). Treatment continued in 28-day cycles until progression, intolerable adverse events (AEs) or other reasons for discontinuation. Primary endpoint was progression-free survival (PFS), with an interim futility analysis incorporated in the study design. Results: Following the results of the interim analysis, the Data Monitoring Committee (DMC) advised early termination of the trial and discontinuation of Xen treatment. Thus, Xen treatment exposure time and time-to-event data for the Xen+Ev+Ex arm are limited. Of the 139 women treated (Xen+Ev+Ex 70; Ev+Ex 69), 77% had VM. Median PFS was not significantly different between arms (Xen+Ev+Ex vs Ev+Ex, 7.3 vs 5.6 months; HR [95% CI] 0.97 [0.57–1.65]; p=0.91). In a pre-specified subgroup of pts without VM, Xen+Ev+Ex showed favorable PFS vs Ev+Ex (HR 0.21 [0.05–0.98]; Pint=0.0141). Pint values Conclusion: In the overall population, PFS did not improve with the addition of Xen to Ev+Ex and the trial was therefore discontinued early. Nevertheless, a favorable signal was observed in the pre-specified subgroup of pts without VM when treated with Xen+Ev+Ex, which warrants additional investigation. The safety profile was comparable between arms. Citation Format: Crown J, Sablin M-P, Cortes J, Bergh J, Im S-A, Lu Y-S, Martinez N, Neven P, Lee KS, Morales S, Perez-Fidalgo JA, Adamson D, Goncalves A, Prat A, Jerusalem G, Schlieker L, Espadero R-M, Bogenrieder T, Chin-Lun Huang D, Schmid P. Xentuzumab (BI 836845), an insulin-like growth factor (IGF)-neutralizing antibody (Ab), combined with exemestane and everolimus in hormone receptor-positive (HR+) locally advanced/metastatic breast cancer (LA/mBC): Randomized phase 2 results [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-01.