Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Lenvatinib+pembrolizumab in patients with advanced endometrial cancer: updated results (#368)

Vicky Makker 1 , Drew Rasco 2 , Nicholas J Vogelzang 3 , Mark Messing 4 , Marcia S Brose 5 , Allen L Cohn 6 , Carol Aghajanian 1 , Daniel E Stepan 7 , Corina Dutcus 7 , Emmett Schmidt 8 , Matthew Guo 7 , Pallavi Sachdev 7 , Robert Shumaker 7 , Louise Young 9 , Matthew Taylor 10
  1. Memorial Sloan Ketting Cancer Center, New York, USA
  2. START, San Antonio, Texas, USA
  3. Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
  4. Texas Oncology, Bedford, TX, USA
  5. Perelman Center for Advanced Medicine, Philadelpha, PA , USA
  6. Rocky Mountain Cancer Center, Denver, CO, USA
  7. Eisai Inc., Woodcliff Lake, New Jersey, United States of America
  8. Merck Co. Inc, Kenilworth, New Jersey, USA
  9. Eisai Australia Pty Ltd, Melbourne, VIC, Australia
  10. Oregon Health and Science University, Portland, Oregon, USA

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 [12], grade 3 [5]; serous [18]; others [8]; unknown [4]). 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.