- Lenvatinib plus pembrolizumab shows promising antitumor activity in patients with advanced melanoma with confirmed progression on programmed cell death ligand 1 (PD-L1) inhibitor.
- No new safety signals were identified.
- The combination represents a potential treatment regimen in this population.
Why this matters
- Safe and effective treatments are needed for melanoma that progresses on programmed cell death 1 (PD-1) or PD-L1 inhibitor.
- Open-label, single-group, phase 2 study (LEAP-004).
- Enrolled patients with unresectable stage III-IV melanoma, progression confirmed per Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) on or within 12 weeks of the last dose of anti-PD-L1 (alone or combined with anticytotoxic T-lymphocyte antigen 4 [CTLA-4] or other therapies).
- 103 patients treated with once-daily lenvatinib 20 mg/day orally and ≤35 doses of pembrolizumab 200 mg intravenously every 3 weeks until progressive disease, unacceptable toxicity, or patient or physician decision.
- Primary endpoint: objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR).
- Secondary endpoints: PFS and duration of response (DOR), OS, and safety.
- Funding: MSD; Eisai Inc.
- Median study follow-up, 12.0 months.
- Confirmed ORR by BICR:
- 21.4% overall (2 complete and 20 partial responses).
- 31.0% (1 complete and 8 partial responses) for patients previously treated with anti-PD-1/L1 + anti-CTLA-4.
- Median DOR, 6.3 months.
- Median PFS: 4.2 months.
- Estimated PFS: 26.2%.
- Median OS: 13.9 months.
- Estimated OS: 65.4%.
- Most common treatment-related adverse event (TRAE): hypertension (56.3%).
- Grade 3-5 TRAEs in 44.7%, grade 5 in 1.0%, and led to discontinuation in 7.8%.
“This combination might be an option for patients whose disease progressed on an anti-PD-1. It is now important for us to understand which patients benefit most from lenvatinib plus pembrolizumab treatment, toward personalised immunotherapy,” said Bartosz Chmielowski, associate clinical professor, Jonsson Comprehensive Cancer Center, University of California Los Angeles, who was not involved in the work.
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