Safety, clinical activity and biomarkers of atezolizumab (atezo) in advanced ovarian cancer (OC)

Background

OC usually presents at an advanced stage and has high rates of recurrence and mortality. Most pts die of drug-resistant OC within 5 y, highlighting the need for new therapies. As OC with high T cell infiltrates at diagnosis has longer OS, we examined atezolizumab (atezo; anti-PDL1) in pts with recurrent OC.

Methods

Pts received atezo IV q3w (0.3-15 mg/kg) in a Ph Ia dose-escalation/expansion study (NCT01375842) and were treated until loss of clinical benefit. Confirmed ORR and PFS were assessed by RECIST v1.1. PD-L1 status on immune cells (IC) was centrally evaluated (VENTANA SP142 IHC assay) and scored as IC0, 1, 2, 3. After dose-escalation, only IC2 or 3 pts were enrolled. Molecular subtyping was performed using nanostring.

Results

As of Dec 15, 2015, 12 pts with ECOG PS 0/1 (50%/50%) and median age of 61 y (range 39-72) were evaluable for safety. 11/12 received ≥ 2 lines of therapy. Atezo doses (mg/kg) were: 0.3 (n = 2), 10 (n = 1) and 15 (n = 9). With a median treatment duration of 2.8 mo, 11/12 pts had a treatment-related AE. These were mainly Gr 1-2; fatigue and pain were most common (5 pts each). 2 pts (17%) had a Gr 3 related AE (autoimmune hepatitis; maculopapular rash). There were no Gr 4 or 5 related AEs or AEs leading to withdrawal. Of 9 response-evaluable pts (10-15 mg/kg atezo and ≥ 12 wk followup; 1 pt without RECIST measurable disease at baseline was evaluable for PFS/OS but not response), 2 pts (22%) had a PR. 1 responder had an 8.1 mo DOR and the other remains on study at 16.6+ mo with a 100% reduction in target lesion volume (1 nontarget lesion remained). 5 pts had PD and 2 were nonevaluable. Median PFS was 2.9 mo (95% CI 1.3-5.5). Median OS was 11.3 mo (95% CI 5.5-27.7) and 17.4 mo (95% CI 5.9-27.7) in 9 IC2/3 pts. Of the 10 evaluable for PFS/OS, 1 pt was IC0/1, 9 were IC2/3 and all belonged to an RNA-defined immunoreactive subgroup of OC that is associated with T cell activation and high PD-L1 expression. Atezo responders were IC2/3 and had low baseline CA125 levels vs pts who progressed.

Conclusions

In this single-agent OC cohort, atezo demonstrated tolerable safety and encouraging clinical activity. Scientifically rational combinations with chemotherapy, targeted therapy or other cancer immunotherapies may augment the clinical benefit of atezo in OC pts.

Clinical trial identification

NCT01375842

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

J.R. Infante: I have no personal conflicts of interest, my institution gets funding for research and consulting from Genentech. L.A. Emens: Grant from Roche/Genentech. A.S. Balmanoukian: speakers bureaus for Merck and BMS. Y. Wang, B. Liu, L. Molinero, M. Fasso, C. O'Hear: Employee of Genentech. All other authors have declared no conflicts of interest.