Clinical activity, safety and biomarker results from a phase Ia study of atezolizumab (atezo) in advanced/recurrent endometrial cancer (rEC).

5585 Background: The prognosis for patients (pts) with rEC remains poor, with a 5-y OS of 20%-26%. We report safety, clinical activity and biomarker data from a Phase Ia study of atezo (anti–PD-L1) monotherapy in rEC. Methods: Atezo 1200 mg or 15 mg/kg IV q3w was administered until toxicity or loss of clinical benefit. Pts were initially eligible based on PD-L1 status ( > 5% of tumor-infiltrating immune cells [IC; IC2/3], VENTANA SP142 IHC assay) and then enrolled regardless of PD-L1 status. Tumor-infiltrating lymphocytes (TILs) were assessed by H&E. The FoundationOne NGS panel was used for microsatellite instability (MSI) and tumor mutation load analyses. Confirmed ORR and PFS were assessed by RECIST v1.1. Results: As of March 31, 2016, 15 pts were evaluable for safety and efficacy (minimum follow-up, 11.2 mo). The median age was 61 y (range, 20-74 y), 53% were ECOG PS 1 and 93% had ≥ 2 prior systemic therapies; 10 (67%) pts had prior RT. Pts were MSI-H (1/15), MSS (7/15) or MSI unknown (7/15). EC subtypes were endometrioid (5/15), serous (5/15), ER+ leiomyosarcoma (1/15) or unknown (4/15). Five (33%) pts were IC2/3, and 10 (67%) pts were IC0/1. Seven (47%) pts had any related AE, mainly G1-2 (5 pts). No G4-5 related AEs occurred. Two pts had related SAEs (colitis; rash). ORR was 13% (2/15) by RECIST. Both pts achieved PR and were IC2/3. ORR for IC2/3 pts was 40% (2/5). One responder was MSS and heavily infiltrated with TILs (IC3, 70% TILs, 1.8 Mut/Mb, unknown subtype); the other responder was hypermutated, MSI-H and moderately infiltrated with TILs (IC2, 10% TILs, 237 Mut/Mb, endometrioid). DOR in the 2 responders was 7.3 and 8.1+ mo. mPFS was 1.7 mo (range, 0.6-11+ mo); mOS was 9.6 mo (range, 0.6-11.8+ mo). Of the remaining pts, 2 had SD, 9 had PD and 2 were non-evaluable. DCR (PR + SD) was 27%. A trend for higher PFS and OS was seen in IC2/3 vs IC0/1 pts. Conclusions: Atezo had a favorable safety profile in rEC, with durable clinical benefit in some pts. Clinical benefit appeared to increase with higher PD-L1 expression, suggesting a link between PD-L1 status and response. Hypermutation and/or high immune infiltration may be linked to response to PD-L1 blockade, and further evaluation is merited. Clinical trial information: NCT01375842.