Abstract
A phase 2 clinical trial of regorafenib in patients with advanced pretreated melanoma (RegoMel).
Author
Iris Dirven
Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium
info_outline
Iris Dirven, Manon Vounckx, Jolien Isabel Kessels, Nathalie Vanlaer, Berlinde von Kemp, Giuseppe Fasolino, Bart Neyns
Full text
Authors
Iris Dirven
Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium
info_outline
Iris Dirven, Manon Vounckx, Jolien Isabel Kessels, Nathalie Vanlaer, Berlinde von Kemp, Giuseppe Fasolino, Bart Neyns
Organizations
Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium, Department of Cardiology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium, Department of Ophthalmology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium, Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium
Abstract Disclosures
Research Funding
Universitair Ziekenhuis Brussel
Background:
A majority of advanced melanoma patients (pts) will eventually progress despite treatment with PD-(L)1/CTLA-4/LAG-3 immune checkpoint- and BRAF-/MEK-inhibitors (BRAF-/MEKi; restricted to
BRAF
V600
-mutant pts). Retrospective case observations indicate activity of regorafenib (REGO) in this setting (1).
Methods:
This single center, prospective, two-stage, phase 2 clinical trial, investigates REGO 80 mg QD (continuous dosing) in pts with advanced melanoma refractory to standard of care treatment. Objective response rate (ORR, by RECIST v1.1) served as the primary endpoint. The sample size (n=16) was determined according to a Simon’s two-stage minimax statistical design; the trial is considered positive if 3 or more responses are observed. Response assessments are performed every 6 weeks (q6w) during the first 24w, and q12w thereafter. Secondary endpoints are safety, progression free survival (PFS) and overall survival (OS). REGO treatment beyond first progression was permitted if considered to be of potential clinical benefit. Database lock was on Jan 9
th
, 2024.
Results:
From Oct 2022 to Sep 2023, 16 pts were enrolled (9 male, med age 61y; AJCC stage IIIC: 1; IV-M1a: 1; -M1c: 12, -M1d: 2, ECOG PS 0-1: 100%). Oncogenic driver mutations were identified in
BRAF
V600
: 7-,
KIT
: 3-,
NF1
: 3-,
NRAS
Q61K
: 2-,
RAF
fusion: 1 pt. The ORR was 31% (: 5 partial responses (PR) - 4 confirmed in 3
KIT-,
and
1
BRAF
V600
-
mut
pt; and
1 unconfirmed in a
BRAF
V600
-mut pt). One
KIT-
mut pt had previously progressed on imatinib. The median duration of response (DoR) was 29.7w (range 12-44). The disease control rate (DCR) was 56%. The median time on REGO monotherapy was 12.3w [95% CI 2.3-22.3], treatment is ongoing in 3 pts. At first progression, 6
BRAF
V600
-mut pts continued REGO in association with BRAF-/MEKi, in 5 response evaluable pts there is an ORR of 40% (2 PR with DoR of 24w and 30w) and DCR of 80%. At database lock, 11 pts were alive with a median follow up of 48.4w (range 24-63), 13 pts have progressed on REGO monotherapy (median PFS 11.9w [95% CI 3.5-20.3]; median OS was not reached). There were no grade ≥ 4 treatment related adverse events (TRAE); 56% of pts had at least one grade 3 TRAE, including hypertension (n=3) and maculo-papular rash (n=2). There was one toxicity-related REGO discontinuation.
Conclusions:
This phase 2 clinical trial on REGO monotherapy in advanced pretreated melanoma patients met its primary endpoint and demonstrated significant anti-tumor activity in
KIT
-mutant melanoma patients. In
BRAF
V600
-mutant melanoma, continuation of REGO in combination with BRAF-/MEK-inhibitors demonstrated promising activity in patients who previously progressed on BRAF-/MEK-inhibitors for which further prospective investigation is ongoing. 1. Dirven I. et al. ESMO Meeting 2023. Clinical trial information: NCT05370807.
Clinical status
Clinical
1 clinical trial
2 organizations
8 drugs
10 targets
Drug
RegorafenibDrug
BRAF-inhibitorsDrug
MEK-inhibitorsDrug
imatinibTarget
KITTarget
BRAFTarget
BRAF V600ETarget
PDGFRATarget
MEK1Target
ABL Myristoyl PocketDrug
CTLA-4Drug
LAG-3Target
CTLA-4Target
PD-1Target
LAG-3Target
PD-L1Organization
Universitair Ziekenhuis BrusselOrganization
Vrije Universiteit BrusselClinical trial
A Phase-2 Clinical Trial of Regorafenib in Patients With Pretreated Advanced Melanoma - Definition of Two Additional Stratified Patient Cohorts of Regorafenib Plus BRAF-/MEK-inhibitors in Pretreated BRAF V600-mutant Melanoma PatientsStatus: Recruiting, Estimated PCD: 2024-12-01