Phase Ib study of anlotinib in combination with anti-PD-L1 antibody (TQB2450) in patients with advanced acral melanoma
© 2023 European Academy of Dermatology and Venereology..
BACKGROUND: Acral melanoma, the most common subtype of melanoma in Asians, is often diagnosed at an advanced stage and responds poorly to current programmed cell death protein 1 (PD-1) inhibitors.
OBJECTIVES: To evaluate the safety and efficacy of TQB2450 and anlotinib in patients with advanced acral melanoma in a phase Ib study (NCT03991975).
METHODS: Patients received TQB2450 (1200 mg every 3 weeks) and anlotinib (10 mg or 12 mg once daily, 2-week on/1-week off) in the dose-escalation and dose-expansion phases. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and objective response rate (ORR).
RESULTS: Nineteen patients were enrolled between June 2019 and June 2022. The majority of patients (16 of 19 patients) received anlotinib and TQB2450 as first-line treatment. No DLTs were observed, and MTD was not reached. Eighteen (94.7%) out of 19 patients experienced treatment-related adverse events (TRAEs), but most were grade 1 or 2. Grade 3 or greater TRAEs occurred in seven patients (36.8%). The ORR was 26.3% (two complete responses and three partial responses). The disease control rate was 73.7%. The median duration of response was 30.3 months [95% confidence interval (CI): 5.8-NA]. The median progression-free survival (PFS) was 5.5 months (95% CI: 2.8-NA), and median overall survival was 20.3 months (95% CI: 14.8-NA). Whole-exome sequencing suggested that acquired drug resistance might be attributed to activation of the MAPK signalling pathway and transformation to an immunosuppressive tumour environment.
CONCLUSIONS: TQB2450 combined with anlotinib showed favourable tolerance and promising anti-tumour activity with a prolonged PFS compared with anti-PD1 monotherapy in patients with advanced acral melanoma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
|---|---|
| Enthalten in: |
Journal of the European Academy of Dermatology and Venereology : JEADV - 38(2024), 1 vom: 21. Jan., Seite 93-101 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Du, Yu [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anlotinib |
|---|
| Anmerkungen: |
Date Completed 19.01.2024 Date Revised 19.01.2024 published: Print-Electronic ClinicalTrials.gov: NCT03991975 Citation Status MEDLINE |
|---|
| doi: |
10.1111/jdv.19467 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM361240120 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM361240120 | ||
| 003 | DE-627 | ||
| 005 | 20240120231822.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/jdv.19467 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1265.xml |
| 035 | |a (DE-627)NLM361240120 | ||
| 035 | |a (NLM)37625814 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Du, Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phase Ib study of anlotinib in combination with anti-PD-L1 antibody (TQB2450) in patients with advanced acral melanoma |
| 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 19.01.2024 | ||
| 500 | |a Date Revised 19.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03991975 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 European Academy of Dermatology and Venereology. | ||
| 520 | |a BACKGROUND: Acral melanoma, the most common subtype of melanoma in Asians, is often diagnosed at an advanced stage and responds poorly to current programmed cell death protein 1 (PD-1) inhibitors | ||
| 520 | |a OBJECTIVES: To evaluate the safety and efficacy of TQB2450 and anlotinib in patients with advanced acral melanoma in a phase Ib study (NCT03991975) | ||
| 520 | |a METHODS: Patients received TQB2450 (1200 mg every 3 weeks) and anlotinib (10 mg or 12 mg once daily, 2-week on/1-week off) in the dose-escalation and dose-expansion phases. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and objective response rate (ORR) | ||
| 520 | |a RESULTS: Nineteen patients were enrolled between June 2019 and June 2022. The majority of patients (16 of 19 patients) received anlotinib and TQB2450 as first-line treatment. No DLTs were observed, and MTD was not reached. Eighteen (94.7%) out of 19 patients experienced treatment-related adverse events (TRAEs), but most were grade 1 or 2. Grade 3 or greater TRAEs occurred in seven patients (36.8%). The ORR was 26.3% (two complete responses and three partial responses). The disease control rate was 73.7%. The median duration of response was 30.3 months [95% confidence interval (CI): 5.8-NA]. The median progression-free survival (PFS) was 5.5 months (95% CI: 2.8-NA), and median overall survival was 20.3 months (95% CI: 14.8-NA). Whole-exome sequencing suggested that acquired drug resistance might be attributed to activation of the MAPK signalling pathway and transformation to an immunosuppressive tumour environment | ||
| 520 | |a CONCLUSIONS: TQB2450 combined with anlotinib showed favourable tolerance and promising anti-tumour activity with a prolonged PFS compared with anti-PD1 monotherapy in patients with advanced acral melanoma | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a anlotinib |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Immune Checkpoint Inhibitors |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Quinolines |2 NLM | |
| 700 | 1 | |a Dai, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xiaoting |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Zhihong |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Chuanliang |e verfasserin |4 aut | |
| 700 | 1 | |a Sheng, Xinan |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Bixia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Xieqiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Siming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Si, Lu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of the European Academy of Dermatology and Venereology : JEADV |d 1997 |g 38(2024), 1 vom: 21. Jan., Seite 93-101 |w (DE-627)NLM091705932 |x 1468-3083 |7 nnns |
| 773 | 1 | 8 | |g volume:38 |g year:2024 |g number:1 |g day:21 |g month:01 |g pages:93-101 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/jdv.19467 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 38 |j 2024 |e 1 |b 21 |c 01 |h 93-101 | ||