Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment : A phase 2 clinical trial (BG01-1801)
© 2023 Published by Elsevier B.V. on behalf of Chinese Medical Association (CMA)..
Background: Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC.
Methods: Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m2 via intravenous injection daily, day 1-5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
Results: From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4-26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%-34.9%) in the intention-to-treat (ITT) cohort (N = 26) and 19.0% (95% CI, 5.4%-41.9%) in the per-protocol (PP) cohort (N = 21). The disease control rate was 69.2% (95% CI, 48.2%-85.7%) and 81.0% (95% CI, 58.1%-94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1-5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50-5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50-9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%-84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications.
Conclusions: In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment.
Trial registration: No.NCT03693547; https://classic.clinicaltrials.gov.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
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| Enthalten in: |
Cancer pathogenesis and therapy - 2(2024), 2 vom: 29. Apr., Seite 103-111 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shi, Yuankai [VerfasserIn] |
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| Links: |
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| Themen: |
Efficacy |
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| Anmerkungen: |
Date Revised 12.04.2024 published: Electronic-eCollection ClinicalTrials.gov: NCT03693547 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.cpt.2023.10.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370908082 |
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| 100 | 1 | |a Shi, Yuankai |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment |b A phase 2 clinical trial (BG01-1801) |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 12.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT03693547 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023 Published by Elsevier B.V. on behalf of Chinese Medical Association (CMA). | ||
| 520 | |a Background: Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC | ||
| 520 | |a Methods: Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m2 via intravenous injection daily, day 1-5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety | ||
| 520 | |a Results: From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4-26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%-34.9%) in the intention-to-treat (ITT) cohort (N = 26) and 19.0% (95% CI, 5.4%-41.9%) in the per-protocol (PP) cohort (N = 21). The disease control rate was 69.2% (95% CI, 48.2%-85.7%) and 81.0% (95% CI, 58.1%-94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1-5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50-5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50-9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%-84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications | ||
| 520 | |a Conclusions: In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment | ||
| 520 | |a Trial registration: No.NCT03693547; https://classic.clinicaltrials.gov | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Efficacy | |
| 650 | 4 | |a Locally advanced or metastatic non-small-cell lung cancer | |
| 650 | 4 | |a Platinum- and taxane-refractory | |
| 650 | 4 | |a Utidelone | |
| 700 | 1 | |a Chen, Gongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yanqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Lin |e verfasserin |4 aut | |
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