Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved..
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 the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636).
PATIENTS AND 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 were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability.
RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths.
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
|---|---|
| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 35(2024), 2 vom: 09. Feb., Seite 221-228 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lewis, K D [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT03132636 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.annonc.2023.10.123 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365629693 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365629693 | ||
| 003 | DE-627 | ||
| 005 | 20240214233002.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.annonc.2023.10.123 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1293.xml |
| 035 | |a (DE-627)NLM365629693 | ||
| 035 | |a (NLM)38072158 | ||
| 035 | |a (PII)S0923-7534(23)04329-6 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lewis, K D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03132636 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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 the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636) | ||
| 520 | |a PATIENTS AND 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 were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability | ||
| 520 | |a RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a PD-1 | |
| 650 | 4 | |a cemiplimab | |
| 650 | 4 | |a hedgehog inhibitor | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a metastatic basal cell carcinoma | |
| 650 | 7 | |a cemiplimab |2 NLM | |
| 650 | 7 | |a 6QVL057INT |2 NLM | |
| 650 | 7 | |a Hedgehog Proteins |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Amides |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Peris, K |e verfasserin |4 aut | |
| 700 | 1 | |a Sekulic, A |e verfasserin |4 aut | |
| 700 | 1 | |a Stratigos, A J |e verfasserin |4 aut | |
| 700 | 1 | |a Dunn, L |e verfasserin |4 aut | |
| 700 | 1 | |a Eroglu, Z |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, A L S |e verfasserin |4 aut | |
| 700 | 1 | |a Migden, M R |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, S-Y |e verfasserin |4 aut | |
| 700 | 1 | |a Mohan, K |e verfasserin |4 aut | |
| 700 | 1 | |a Coates, E |e verfasserin |4 aut | |
| 700 | 1 | |a Okoye, E |e verfasserin |4 aut | |
| 700 | 1 | |a Bowler, T |e verfasserin |4 aut | |
| 700 | 1 | |a Baurain, J-F |e verfasserin |4 aut | |
| 700 | 1 | |a Bechter, O |e verfasserin |4 aut | |
| 700 | 1 | |a Hauschild, A |e verfasserin |4 aut | |
| 700 | 1 | |a Butler, M O |e verfasserin |4 aut | |
| 700 | 1 | |a Hernandez-Aya, L |e verfasserin |4 aut | |
| 700 | 1 | |a Licitra, L |e verfasserin |4 aut | |
| 700 | 1 | |a Neves, R I |e verfasserin |4 aut | |
| 700 | 1 | |a Ruiz, E S |e verfasserin |4 aut | |
| 700 | 1 | |a Seebach, F |e verfasserin |4 aut | |
| 700 | 1 | |a Lowy, I |e verfasserin |4 aut | |
| 700 | 1 | |a Goncalves, P |e verfasserin |4 aut | |
| 700 | 1 | |a Fury, M G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of oncology : official journal of the European Society for Medical Oncology |d 1990 |g 35(2024), 2 vom: 09. Feb., Seite 221-228 |w (DE-627)NLM012606308 |x 1569-8041 |7 nnns |
| 773 | 1 | 8 | |g volume:35 |g year:2024 |g number:2 |g day:09 |g month:02 |g pages:221-228 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.annonc.2023.10.123 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 35 |j 2024 |e 2 |b 09 |c 02 |h 221-228 | ||