Aim:
Lenvatinib (LEN), an inhibitor of VEGFR 1−3, FGFR 1−4, PDGFRα, RET, and KIT, was approved in combination with everolimus to treat advanced renal cell carcinoma (RCC) after 1 prior VEGF-targeted treatment. We report results for the RCC cohort of a phase 1b/2 trial of LEN+pembrolizumab in patients with selected solid tumors.
Methods:
This was a multicenter open-label study. Patients had metastatic clear cell RCC, measurable disease per immune-related RECIST (irRECIST) and ECOG PS ≤1. LEN 20 mg/d plus pembrolizumab 200 mg intravenously every 3 weeks was assessed as the MTD and recommended phase 2 dose in phase 1b. Tumor assessments were performed by trial investigators using irRECIST. The primary phase 2 endpoint was ORR at 24 weeks. Secondary endpoints included ORR, PFS, and DOR.
Results:
Thirty patients were enrolled in either the phase 1b (n=8) or phase 2 cohort (n=22). Data cutoff was February 15, 2017. Eleven (37%) patients had 0, 11 (37%) had 1, and 8 (27%) had ≥2 prior anti-cancer therapies. Of patients who received prior medication (n=19, 63%), 16 (53%) received prior VEGF-targeted therapy. Efficacy outcomes are in the table. At data cutoff, 17 (57%) patients were receiving treatment, 8 (27%) completed treatment due to disease progression, and 5 (17%) discontinued. Most common any-grade TEAEs were diarrhea, fatigue, hypothyroidism, nausea, and stomatitis. Toxicities were manageable with dose interruption and/or modification, and no new safety signals were found. Updated data will be presented.
Conclusion:
LEN+pembrolizumab combination treatment showed promising antitumor activity and an acceptable safety profile. A phase 3 trial of LEN+pembrolizumab and LEN+everolimus, vs sunitinib in first-line treatment for metastatic clear cell RCC is ongoing.
|
Outcome |
n=30 |
95% CI |
|
ORR, n (%) |
19 (63.3) |
43.9%–80.1% |
|
Median PFS, mos |
NE |
9.9–NE |
|
Median DOR, mos |
NE |
8.4–NE |
|
NE, not estimable. |