Aims: Lenvatinib, a multikinase inhibitor of VEGFR and other targets, is approved in combination with everolimus for advanced renal cell carcinoma (RCC) after 1 prior VEGF-targeted therapy.
Methods: In this multicenter, open-label, phase 1b/2 study (NCT02501096), patients with metastatic clear cell RCC and measurable disease per immune-related RECIST (irRECIST) received oral lenvatinib 20 mg/day + pembrolizumab 200 mg Q3W, IV. Tumor assessments were by study investigators using irRECIST, with retrospective independent radiographic review (IRR) per irRECIST and RECIST v1.1. The phase 2 primary endpoint was objective response rate at 24 weeks (ORRWK24).
Results: 30 Patients were enrolled: 12 (40%) had 0 and 18 (60%) had ≥1 prior anticancer therapy; 16 (53%) received ≥1 prior VEGF-targeted therapy. At data cutoff (August 1, 2017), median follow-up for progression-free survival (PFS) was 13.8 months (95% CI, 11.9–15.7). ORRWK24 (per investigator, irRECIST) was 63.3% (95% CI, 43.9–80.1). ORR (per IRR, RECIST v1.1) was 66.7% (95% CI, 47.2–82.7); median PFS was 17.7 months (95% CI, 9.6–NE). Efficacy outcomes are below (Table). Grade 3/4 adverse events (AEs) occurred in 21 (70%) patients; 4 (13%) discontinued treatment due to AEs. The most common AEs were diarrhea (83%), fatigue (70%), hypothyroidism (67%), stomatitis (63%), and nausea (60%).
Conclusions: Lenvatinib+pembrolizumab showed promising antitumor activity with manageable AEs, and no new safety signals were identified. A phase 3 study of lenvatinib+pembrolizumab and lenvatinib+everolimus versus sunitinib for the first-line treatment of advanced RCC is underway (NCT02811861).
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Outcome |
N=30 |
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IRR |
Investigator review |
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RECIST v1.1 |
irRECIST |
irRECIST |
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ORR*, n (%) 95% CI |
20 (66.7) 47.2–82.7 |
20 (66.7) 47.2–82.7 |
21 (70.0) 50.6–85.3 |
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Median duration of response, months 95% CI |
16.3 8.9–NE |
NE 14.9–NE |
18.4 10.3–NE |
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Median PFS, months 95% CI |
17.7 9.6–NE |
17.7 10.2–NE |
19.8 11.6–NE |
*Overall ORR.
NE, not estimable.