Ana Maria Arance Fernandez, MD of Hospital ClÃnic de Barcelona, Barcelona, Spain speaks on her ESMO abstract – LBA44 – Lenvatinib (len) plus pembrolizumab (pembro) for advanced melanoma (MEL) that progressed on a PD-1 or PD-L1 inhibitor: Initial results of LEAP-004.
Context
Identification of safe and reliable MEL treatment options that have advanced towards anti-PD-1-based treatment
A major unmet need is counseling. The single-arm, open-label, step 2 LEAP-004 analysis
The combination of len (multikinase inhibitor) and pembro (anti-PD-1) is evaluated by (NCT03776136) in
Such a nation.
Methodology
Qualified pts had unresectable stage III-IV MEL, PD confirmed by iRECIST within 12 wk of last stage III-IV MEL, PD confirmed by iRECIST
PD-1 / L1 inhibitor dose given alone or with anti-CTLA-4 or other ⇠2 dose therapies,
Measurable illness, and PS 0/1 of ECOG. Len 20 mg / d PO QD + ~35 doses of pembro were obtained by Pts
200 mg IV Q3W up to PD or inappropriate toxicity; beyond PD, qualifying pts could be treated. Imagery
Q9W through wk 54, Q12W through wk 102, and subsequently Q24W are performed. The main termination point is
Blinded Independent Central Review (BICR) ORR per RECIST v1.1. The secondary end-points are
By BICR, OS, and protection, PFS and DOR per RECIST v1.1.
Outcomes
103 pts were enrolled and treated from Feb to Sept 2019; the median age was 63 y, 67.0 percent had stage age.
55.3 percent had LDH > ULN (20.4 percent ⇠2 ⇠ULN) and 36.9 percent had BRAFV600 mutation. M1c / M1d disease
61.2 percent received ~2 prior MEL therapies, 32.0 percent received prior BRAF ± MEK inhibition, and 28.2 percent received prior MEL inhibition
The previous anti-PD-1 / L1 + anti-CTLA-4 had PD. The median follow-up time for the analysis was 12.0 mo (range 8.7-15.6).
BICR ‘s verified ORR was 21.4 percent (95 percent CI 13.9-30.5; 2 CRs, 20 PRs) overall and 31.0 percent overall, respectively.
(15.3-50.8; 1 CR, 8 PRs) on previous anti-PD-1 / L1 + anti-CTLA-4 for pts with PD. The DCR stood at 65.0%.
Median DOR was 6.3 mo (range 2.1 + -11.1 +); DOR ⇠6 mo KM estimate was 72.6 percent. Median (95% Median)
4.2 mo (3.5-6.3) and 13.9 mo (95 percent CI 10.8-NR) were CI) PFS and OS. Estimates of the 9-mo PFS and OS
26.2 percent and 65.4 percent were. Hypertension was the most common treatment-related AE (TRAE) (56.3 percent),
Diarrhea (35.9 percent), and (34.0 percent) nausea. TRAEs were 44.7 percent gr 3-5 and 1.0 percent gr 5 and led to
7.8 percent discontinuation of Len and/or Pembro.
Findings
The combination of len and pembro has operation with reported MEL in pts with advanced MEL
Progression on an inhibitor of PD-1 / L1, including those with PD on combined anti-PD-1 / L1++
Anti-The CTLA-4. The safety profile was in line with previous studies. Such information support len+pembro
For this population with high unmet need, as a possible regimen.
Identification of Clinical Trial
Originally posted on December 14, 2018, NCT03776136.