Journal article
Phase 1b study of immunocytokine simlukafusp alfa (FAP-IL2v) combined with pembrolizumab for treatment of advanced and/or metastatic melanoma
Cancer research communications, Vol.5(2), pp.358-368
02/01/2025
DOI: 10.1158/2767-9764.CRC-24-0601
PMCID: PMC11848832
PMID: 39895413
Abstract
This study explored the combination of FAP-IL2v, a novel immune-cytokine, with pembrolizumab in patients with advanced and/or metastatic melanoma.
This open-label, multicenter, phase 1b clinical study (NCT03875079) evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics (PK), and antitumor activity of FAP-IL2v (simlukafusp alfa, RO6874281) in combination with pembrolizumab. Patients with advanced and/or metastatic melanoma were either checkpoint inhibitor (CPI)-naïve or -experienced. Patients received 10 mg FAP-IL2v either continuously once every three weeks (Q3W) or in an induction/maintenance setting consisting of a 3-week induction phase with weekly (QW) dosing followed by continuous Q3W dosing. Pembrolizumab was dosed Q3W at 200 mg.
Eighty-three patients were treated, 16 patients in two safety run-in cohorts, and 67 patients in two extension cohorts; 75 (90.4%) patients were CPI-experienced. The PK of FAP-IL2v in combination with pembrolizumab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded NK and CD8 T cells. The most common FAP-IL2v-related grade 3/4 AEs were lymphopenia (23%), elevated γ‑glutamyltransferase (8%), elevated alanine aminotransferase (6%), and infusion-related reaction (6%). A response was observed in 5 of 75 (6.7%) CPI-experienced patients (all partial responses) and in 2 of 8 CPI-naïve patients (one complete, one partial response). The median progression-free survival was 3.1 months.
The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity.
Details
- Title: Subtitle
- Phase 1b study of immunocytokine simlukafusp alfa (FAP-IL2v) combined with pembrolizumab for treatment of advanced and/or metastatic melanoma
- Creators
- Eva Munoz-Couselo - Vall d'Hebron Institute of OncologyAinara Soria Rivas - Hospital Ramon y Cajal, Madrid, SpainShahneen Sandhu - Peter MacCallum Cancer CentreGeorgina V Long - The University of SydneyMiguel F Sanmamed - Clinica Universidad de NavarraAnna Spreafico - Princess Margaret Cancer CentreElizabeth Buchbinder - Dana-Farber Cancer InstituteMario Sznol - Yale UniversityHans Prenen - Antwerp University HospitalAlexander Fedenko - P.A. Gertsen Moscow Oncology Research Institute, Moscow, RussiaMohammed Milhem - University of Iowa Hospitals and ClinicsAna Maria Arance Fernandez - Hospital Clínic de BarcelonaJean-Jacques Grob - Aix Marseille University, Marseille CEDEX 05, FranceLev Demidov - Russian Cancer Research Center NN BlokhinCaroline Robert - Institut Gustave RoussyChristin Habigt - Roche Pharma AGStefan Evers - RocheNassim Sleiman - RocheDavid Dejardin - RocheCaroline Ardeshir - RocheNicole Martin - RocheChristophe Boetsch - RocheJehad Charo - RocheVolker Teichgraeber - Roche (Switzerland), Basel, SwitzerlandAnton Kraxner - RocheNino Keshelava - RocheOliver Bechter - Universitair Ziekenhuis Leuven
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.5(2), pp.358-368
- DOI
- 10.1158/2767-9764.CRC-24-0601
- PMID
- 39895413
- PMCID
- PMC11848832
- NLM abbreviation
- Cancer Res Commun
- ISSN
- 2767-9764
- eISSN
- 2767-9764
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- F. Hoffmann-La Roche Ltd. - F. Hoffmann-La Roche Ltd.
This study was funded by F. Hoffmann-La Roche Ltd. No grant numbers apply. The authors would like to thank the patients, their families, and the participating study centers. Medical writing assistance was provided by Christian Seitz, PhD, and was funded by F. Hoffmann-La Roche Ltd.
- Language
- English
- Electronic publication date
- 02/03/2025
- Date published
- 02/01/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984786446402771
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