Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

PD-1 cemiplimab hedgehog inhibitor immunotherapy metastatic basal cell carcinoma

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
08 Dec 2023
Historique:
received: 03 04 2023
revised: 06 10 2023
accepted: 10 10 2023
medline: 11 12 2023
pubmed: 11 12 2023
entrez: 10 12 2023
Statut: aheadofprint

Résumé

Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks binding of programmed cell death-1 (PD-1) to its ligands, PD-L1 and PD-L2. Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitors (HHIs) (NCT03132636). In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints included ORR per investigator assessment (INV), progression-free survival (PFS), overall survival (OS), complete response (CR) rate, safety and tolerability. Fifty-four patients were enrolled (70% male, median age 64 years [interquartile range (IQR) 57.0-73.0]). Median duration of follow-up was 8 months (IQR 4-21). ORR per ICR was 22% (95% confidence interval [CI] 12-36), with two CRs and 10 partial responses. Among responders, median time to response per ICR was 3 months (IQR 2-7). Estimated median DOR per ICR was not reached (95% CI 10 months-not evaluable [NE]). Disease control rate was 63% (95% CI 49-76) per ICR and 70% (95% CI 56-82) per INV. Median PFS per ICR was 10 months (95% CI 4-16); median OS was 50 months (95% CI 28-NE). The most common treatment-emergent adverse events were fatigue (23 [43%]) and diarrhoea (20 [37%]). There were no treatment-related deaths. Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Sections du résumé

BACKGROUND BACKGROUND
Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks binding of programmed cell death-1 (PD-1) to its ligands, PD-L1 and PD-L2. Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitors (HHIs) (NCT03132636).
PATIENTS AND METHODS METHODS
In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints included ORR per investigator assessment (INV), progression-free survival (PFS), overall survival (OS), complete response (CR) rate, safety and tolerability.
RESULTS RESULTS
Fifty-four patients were enrolled (70% male, median age 64 years [interquartile range (IQR) 57.0-73.0]). Median duration of follow-up was 8 months (IQR 4-21). ORR per ICR was 22% (95% confidence interval [CI] 12-36), with two CRs and 10 partial responses. Among responders, median time to response per ICR was 3 months (IQR 2-7). Estimated median DOR per ICR was not reached (95% CI 10 months-not evaluable [NE]). Disease control rate was 63% (95% CI 49-76) per ICR and 70% (95% CI 56-82) per INV. Median PFS per ICR was 10 months (95% CI 4-16); median OS was 50 months (95% CI 28-NE). The most common treatment-emergent adverse events were fatigue (23 [43%]) and diarrhoea (20 [37%]). There were no treatment-related deaths.
CONCLUSIONS CONCLUSIONS
Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Identifiants

DOI: 10.1016/j.annonc.2023.10.123 PMID: 38072158
pubmed: 38072158
pii: S0923-7534(23)04329-6
doi: 10.1016/j.annonc.2023.10.123
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT03132636']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Auteurs

K D Lewis (KD)

Department of Medicine-Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA;. Electronic address: karl.lewis@regeneron.com.

K Peris (K)

Department of Medicine and Translational Surgery, Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy;; Department of Medical and Surgical Sciences, Dermatology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.

A Sekulic (A)

Department of Dermatology, Mayo Clinic, Scottsdale, AZ, USA.

A J Stratigos (AJ)

First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece.

L Dunn (L)

Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Z Eroglu (Z)

Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.

A L S Chang (ALS)

Dermatology Department, Stanford University School of Medicine, Redwood City, CA, USA.

M R Migden (MR)

Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

S-Y Yoo (SY)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

K Mohan (K)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

E Coates (E)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

E Okoye (E)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

T Bowler (T)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

J-F Baurain (JF)

Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium.

O Bechter (O)

Department of General Medical Oncology, University Hospitals, Leuven, Belgium.

A Hauschild (A)

Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.

M O Butler (MO)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

L Hernandez-Aya (L)

Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

L Licitra (L)

Department of Medical Oncology Head and Neck Cancer, Istituto Nazionale dei Tumori, Milan, Italy;; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

R I Neves (RI)

Division of Plastic Surgery, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.

E S Ruiz (ES)

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

F Seebach (F)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

I Lowy (I)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

P Goncalves (P)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

M G Fury (MG)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

Classifications MeSH