Aims: Lenvatinib is an inhibitor of VEGFR 1−3, FGFR 1−4, and other kinases. Pembrolizumab is an anti-PD-1 antibody. We report updated interim results from a phase 1b/2 study evaluating lenvatinib+pembrolizumab in advanced endometrial cancer (EC) (NCT02501096).
Methods: In this multicenter, open-label study, patients with histologically confirmed EC irrespective of microsatellite instability (MSI)/mismatch repair (MMR) status and measurable disease, received lenvatinib 20 mg PO QD plus pembrolizumab 200 mg Q3W, IV. Tumor assessments were by investigators using immune-related RECIST (irRECIST). The primary phase 2 endpoint was objective response rate at 24 weeks (ORRWK24). Secondary endpoints included ORR, progression-free survival (PFS), and duration of response (DOR).
Results: At data cutoff (August 1, 2017), 54 patients were enrolled (endometrioid: grade 1 [n=7], grade 2 , grade 3 ; serous ; others ; unknown ). Three (6%) patients were MSI-high (MSI-H); 43 (80%) were non-MSI-H/proficient MMR (MMRp); 8 (15%) were unknown. Median follow-up for PFS was 4.0 months (95% CI, 2.7–7.6). ORRWK24 was 50.0% (95% CI, 32.4–67.6); ORR was 36.7% (95% CI, 23.4–51.7), reflecting the short follow-up for patients with later enrollment. Median DOR has not been reached (95% CI, 4.1– not estimable [NE]); median PFS was 10.1 months (95% CI, 5.3–NE). Of the 3 MSI-H patients, 1 achieved partial response, 1 had stable disease, and 1 had progressive disease. For non-MSI-H/MMRp patients, ORRWK24 was 50.0% (95% CI, 29.9–70.1). Grade 3 treatment-related adverse events (TRAEs) occurred in 32 (59%) patients, with no grade 4 TRAEs. 3 (6%) Patients discontinued treatment due to TRAEs. The most common TRAEs were hypertension (59%), fatigue (50%), diarrhea (44%), hypothyroidism (35%), and stomatitis (33%).
Conclusions: Lenvatinib+pembrolizumab demonstrated encouraging activity in advanced EC regardless of MSI/MMR status, with no new safety signals identified. A randomized, international, 2-arm, phase 3 study in recurrent EC is planned.