A phase II clinical trial of camrelizumab (CAM, an IgG4 antibody against PD-1) combined with apatinib (APA, a VEGFR-2 tyrosine kinase inhibitor) and temozolomide (TMZ) as the first-line treatment for patients (pts) with advanced acral melanoma (AM)
9508 Background: PD-1 monotherapy as the first line stand treatment for advanced melanoma yields an objective response rate (ORR) of < 20% in AM. Although multiple clinical trials are ongoing testing TMZ/APA, TMZ/PD-1 and APA/PD-1 combo therapies in AM, the reported ORR (range 17-23.8%) are far f...
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Published in | Journal of clinical oncology Vol. 40; no. 16_suppl; p. 9508 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.06.2022
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Online Access | Get full text |
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Abstract | 9508
Background: PD-1 monotherapy as the first line stand treatment for advanced melanoma yields an objective response rate (ORR) of < 20% in AM. Although multiple clinical trials are ongoing testing TMZ/APA, TMZ/PD-1 and APA/PD-1 combo therapies in AM, the reported ORR (range 17-23.8%) are far from satisfactory. We therefore conducted a phase II study of CAM/APA/TMZ combo in this subtype aiming for improved efficacy. Methods: We performed a single center, single arm phase II study (NCT04397770) testing the efficacy and safety of CAM/APA/TMZ combo as first-line therapy in pts with advanced AM. The primary endpoint was ORR per RECIST1.1, secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. All pts received iv CAM (200mg q2w), iv TMZ (200mg/m2 d1-5, q4w) and po APA (250mg qd) until disease progression or intolerable toxicity. Results: By Jan 2022, fifty pts were enrolled (48 evaluable), the median follow-up was 12.1 mo (IQR 8.4-14.5). Thirty-one pts achieved CR/PR as the best response (including 1 CR and 30 PR), the ORR was 64.6% (95% CI 49.4-77.4%). The DCR was 95.8% (95%CI, 84.6-99.3%). Both the median PFS and OS was not reached (NR); 6-mo and 12-mo PFS rate was 81.7% (95%CI 71.6-93.3%) and 62.9% (95%CI 48.4-81.7%), respectively; 12-mo OS rate was 82.3% (95%CI 68.2-99.2%). The incidence of treatment-related adverse events (TRAEs) was 94% (47/50). Of 50 patients, the most common grade ≥3 TRAEs included γ-glutamyl transferase elevation (24.0%), direct bilirubin elevation (22.0%), aspartase transaminase elevation (20.0%), alanine transaminase elevation (16.0%), and hypertriglyceridemia (14.0%). No treatment-related deaths occurred. Conclusions: The CAM/APA/TMZ combination demonstrated promising efficacy as the first-line treatment for pts with advanced AM, and was generally well tolerated. Phase III randomized control trial is warranted. Clinical trial information: NCT04397770. |
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AbstractList | 9508
Background: PD-1 monotherapy as the first line stand treatment for advanced melanoma yields an objective response rate (ORR) of < 20% in AM. Although multiple clinical trials are ongoing testing TMZ/APA, TMZ/PD-1 and APA/PD-1 combo therapies in AM, the reported ORR (range 17-23.8%) are far from satisfactory. We therefore conducted a phase II study of CAM/APA/TMZ combo in this subtype aiming for improved efficacy. Methods: We performed a single center, single arm phase II study (NCT04397770) testing the efficacy and safety of CAM/APA/TMZ combo as first-line therapy in pts with advanced AM. The primary endpoint was ORR per RECIST1.1, secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. All pts received iv CAM (200mg q2w), iv TMZ (200mg/m2 d1-5, q4w) and po APA (250mg qd) until disease progression or intolerable toxicity. Results: By Jan 2022, fifty pts were enrolled (48 evaluable), the median follow-up was 12.1 mo (IQR 8.4-14.5). Thirty-one pts achieved CR/PR as the best response (including 1 CR and 30 PR), the ORR was 64.6% (95% CI 49.4-77.4%). The DCR was 95.8% (95%CI, 84.6-99.3%). Both the median PFS and OS was not reached (NR); 6-mo and 12-mo PFS rate was 81.7% (95%CI 71.6-93.3%) and 62.9% (95%CI 48.4-81.7%), respectively; 12-mo OS rate was 82.3% (95%CI 68.2-99.2%). The incidence of treatment-related adverse events (TRAEs) was 94% (47/50). Of 50 patients, the most common grade ≥3 TRAEs included γ-glutamyl transferase elevation (24.0%), direct bilirubin elevation (22.0%), aspartase transaminase elevation (20.0%), alanine transaminase elevation (16.0%), and hypertriglyceridemia (14.0%). No treatment-related deaths occurred. Conclusions: The CAM/APA/TMZ combination demonstrated promising efficacy as the first-line treatment for pts with advanced AM, and was generally well tolerated. Phase III randomized control trial is warranted. Clinical trial information: NCT04397770. |
Author | Li, Caili Cui, Chuanliang Zhou, Li Wang, Xuan Li, Juan Li, Siming Pang, Zheng Si, Lu Kong, Yan Tang, Bixia Lian, Bin Dai, Jie Chi, Zhihong Yan, Xieqiao Yang, Fan Bai, Xue Wei, Xiaoting Guo, Jun Mao, Lili Sheng, Xinan |
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Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China – sequence: 5 givenname: Lili surname: Mao fullname: Mao, Lili organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 6 givenname: Chuanliang surname: Cui fullname: Cui, Chuanliang organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 7 givenname: Zhihong surname: Chi fullname: Chi, Zhihong organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 8 givenname: Xinan surname: Sheng fullname: Sheng, Xinan organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China – sequence: 9 givenname: Bin surname: Lian fullname: Lian, Bin organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 10 givenname: Xuan surname: Wang fullname: Wang, Xuan organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 11 givenname: Bixia surname: Tang fullname: Tang, Bixia organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 12 givenname: Xieqiao surname: Yan fullname: Yan, Xieqiao organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China – sequence: 13 givenname: Siming surname: Li fullname: Li, Siming organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China – sequence: 14 givenname: Yan surname: Kong fullname: Kong, Yan organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 15 givenname: Jie surname: Dai fullname: Dai, Jie organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 16 givenname: Xiaoting surname: Wei fullname: Wei, Xiaoting organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China – sequence: 17 givenname: Juan surname: Li fullname: Li, Juan organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China – sequence: 18 givenname: Fan surname: Yang fullname: Yang, Fan organization: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China – sequence: 19 givenname: Zheng surname: Pang fullname: Pang, Zheng organization: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China – sequence: 20 givenname: Jun surname: Guo fullname: Guo, Jun organization: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China |
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Background: PD-1 monotherapy as the first line stand treatment for advanced melanoma yields an objective response rate (ORR) of < 20% in AM. Although... |
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Title | A phase II clinical trial of camrelizumab (CAM, an IgG4 antibody against PD-1) combined with apatinib (APA, a VEGFR-2 tyrosine kinase inhibitor) and temozolomide (TMZ) as the first-line treatment for patients (pts) with advanced acral melanoma (AM) |
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