Aims
LEN is a multikinase VEGFR inhibitor approved for use in combination with everolimus to treat advanced RCC following VEGF-targeted therapy. PEMBRO is an anti-PD-1 antibody. We report results of an interim analysis of the RCC cohort of a phase 2 trial of LEN+PEMBRO, in patients who progressed with prior ICI therapy.
Methods
This is a per-protocol interim analysis of an open-label study for patients with mccRCC, ≥1 prior therapy, RECIST disease progression on/following an ICI regimen (confirmed ≥4 weeks later), measurable disease, and ECOG PS ≤1. Patients received LEN 20mg/day orally QD plus PEMBRO 200mg intravenously Q3W until toxicity or disease progression. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks.
Results
At data-cutoff (March 29, 2019), the first 33 enrolled patients were followed for ≥12 weeks for response evaluation, and 24 (73%) patients were still on study treatment. The ORR was 51.5%, the DCR was 93.9%, and most patients had tumor shrinkage. Median follow-up time for PFS was 4.2 months. Patient characteristics are summarized (table). ORR (investigator by irRECIST) was 51.5% (95% CI, 33.5–69.2) and median PFS was NE. The most common treatment-related adverse events were fatigue (49%), dysphonia (36%), and diarrhea (33%). Three (9%) patients discontinued treatment due to adverse events.
Conclusions
For patients with mccRCC who progressed during/following ICI therapy, LEN+PEMBRO demonstrated promising antitumor activity. No new safety signals were detected. The study will continue to full cohort expansion.
|
Patient Characteristics, n (%) |
LEN+PEMBRO (n=33) |
|
Prior anticancer regimens |
|
|
1 prior regimen |
14 (42) |
|
>1 prior regimen |
19 (58) |
|
Prior VEGF-targeted therapy |
26 (78.8) |
|
Prior ICI therapy |
33 (100) |
|
PD-1/PD-L1 monotherapy |
14 (42.4) |
|
with VEGF agents |
9 (27.7) |
|
nivolumab + ipilimumab |
7 (21.2) |
|
with other agents |
2 (6.1) |
|
PD-L1 positive |
12 (36.4)* |
|
*30.3% were negative and 33.3% were not available.
|