The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial
PurposeThis multicenter, open-label, phase Ib/II study aimed to assess the efficacy and safety of cadonilimab, a humanized, tetravalent, bispecific antibody plus lenvatinib in first-line treatment of advanced hepatocellular carcinoma (aHCC).MethodsPatients with histologically confirmed aHCC were inc...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238667/full |
| _version_ | 1797652117045903360 |
|---|---|
| author | Qian Qiao Chun Han Sisi Ye Juan Li Guoliang Shao Yuxian Bai Aibing Xu Meili Sun Wei Wang Jian Wu Ming Huang Lijie Song Luke Huang Ting Liu Wei Liu Zhongmin Maxwell Wang Baiyong Li Michelle Xia Li Bai Li Bai |
| author_facet | Qian Qiao Chun Han Sisi Ye Juan Li Guoliang Shao Yuxian Bai Aibing Xu Meili Sun Wei Wang Jian Wu Ming Huang Lijie Song Luke Huang Ting Liu Wei Liu Zhongmin Maxwell Wang Baiyong Li Michelle Xia Li Bai Li Bai |
| author_sort | Qian Qiao |
| collection | DOAJ |
| description | PurposeThis multicenter, open-label, phase Ib/II study aimed to assess the efficacy and safety of cadonilimab, a humanized, tetravalent, bispecific antibody plus lenvatinib in first-line treatment of advanced hepatocellular carcinoma (aHCC).MethodsPatients with histologically confirmed aHCC were included to receive either 6 mg/kg cadonilimab every 2 weeks plus lenvatinib (cohort A) or 15 mg/kg cadonilimab every 3 weeks plus lenvatinib (cohort B). The primary endpoint was objective response rate (ORR) by RECIST v1.1, while the secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and time to response (TTR).ResultsA total of 59 patients were enrolled (31 in cohort A and 28 in cohort B). The median follow-up time was 27.4 months as of the data cutoff date (July 28, 2023). The ORR in cohort A was 35.5% (95% CI: 19.2, 54.6) and that in cohort B was 35.7% (95% CI: 18.6, 55.9), and the median DoR was 13.6 months (95% CI: 4.14, NE) and 13.67 months (95% CI: 3.52, NE), respectively. The median PFS was 8.6 months (95% CI: 5.2, 15.2) and 9.8 months (95% CI: 6.9, 15.2), respectively. The median OS was 27.1 months (95% C: 15.7, NE) for cohort A, while it was not reached for cohort B. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 66.1% of patients, with serious TRAEs occurring in 39.0% of cases. Decreased platelet count (47.5%), proteinuria (45.8%), hypertension (44.1%), and white blood cell count (44.1%) were the most common TRAEs.ConclusionThis novel combination therapy showed promising efficacy and manageable toxicity that could provide an option in first-line setting of aHCC.Clinical Trial Registration[www.ClinicalTrials.gov], NCT04444167. |
| first_indexed | 2024-03-11T16:25:25Z |
| format | Article |
| id | doaj.art-a386c0539f84403aa254ac0265586350 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T16:25:25Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a386c0539f84403aa254ac02655863502023-10-24T13:09:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12386671238667The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trialQian Qiao0Chun Han1Sisi Ye2Juan Li3Guoliang Shao4Yuxian Bai5Aibing Xu6Meili Sun7Wei Wang8Jian Wu9Ming Huang10Lijie Song11Luke Huang12Ting Liu13Wei Liu14Zhongmin Maxwell Wang15Baiyong Li16Michelle Xia17Li Bai18Li Bai19Chinese People’s Liberation Army (PLA) Medical School, Beijing, ChinaDaytime Chemotherapy Center, Beijing Arion Cancer Center, Beijing, ChinaDepartment of Medical Oncology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Medical Oncology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, ChinaIntervention Department, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Medical Oncology, Nantong Tumor Hospital, Nantong, ChinaDepartment of Medical Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Gastroenterology and Urology II, Hunan Cancer Hospital, Changsha, ChinaDepartment of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China0Intervention Department, Yunnan Cancer Hospital&The Third Affiliated Hospital of Kunming Medical University&Yunnan Cancer Center, Kunming, China1Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China2Akeso Biopharma, Inc., Zhongshan, China2Akeso Biopharma, Inc., Zhongshan, China2Akeso Biopharma, Inc., Zhongshan, China2Akeso Biopharma, Inc., Zhongshan, China2Akeso Biopharma, Inc., Zhongshan, China2Akeso Biopharma, Inc., Zhongshan, ChinaChinese People’s Liberation Army (PLA) Medical School, Beijing, ChinaDepartment of Medical Oncology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, ChinaPurposeThis multicenter, open-label, phase Ib/II study aimed to assess the efficacy and safety of cadonilimab, a humanized, tetravalent, bispecific antibody plus lenvatinib in first-line treatment of advanced hepatocellular carcinoma (aHCC).MethodsPatients with histologically confirmed aHCC were included to receive either 6 mg/kg cadonilimab every 2 weeks plus lenvatinib (cohort A) or 15 mg/kg cadonilimab every 3 weeks plus lenvatinib (cohort B). The primary endpoint was objective response rate (ORR) by RECIST v1.1, while the secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and time to response (TTR).ResultsA total of 59 patients were enrolled (31 in cohort A and 28 in cohort B). The median follow-up time was 27.4 months as of the data cutoff date (July 28, 2023). The ORR in cohort A was 35.5% (95% CI: 19.2, 54.6) and that in cohort B was 35.7% (95% CI: 18.6, 55.9), and the median DoR was 13.6 months (95% CI: 4.14, NE) and 13.67 months (95% CI: 3.52, NE), respectively. The median PFS was 8.6 months (95% CI: 5.2, 15.2) and 9.8 months (95% CI: 6.9, 15.2), respectively. The median OS was 27.1 months (95% C: 15.7, NE) for cohort A, while it was not reached for cohort B. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 66.1% of patients, with serious TRAEs occurring in 39.0% of cases. Decreased platelet count (47.5%), proteinuria (45.8%), hypertension (44.1%), and white blood cell count (44.1%) were the most common TRAEs.ConclusionThis novel combination therapy showed promising efficacy and manageable toxicity that could provide an option in first-line setting of aHCC.Clinical Trial Registration[www.ClinicalTrials.gov], NCT04444167.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238667/fullcadonilimablenvatinibBsAbi-specific antibodyhepatocellular carcinomaHCC |
| spellingShingle | Qian Qiao Chun Han Sisi Ye Juan Li Guoliang Shao Yuxian Bai Aibing Xu Meili Sun Wei Wang Jian Wu Ming Huang Lijie Song Luke Huang Ting Liu Wei Liu Zhongmin Maxwell Wang Baiyong Li Michelle Xia Li Bai Li Bai The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial Frontiers in Immunology cadonilimab lenvatinib BsA bi-specific antibody hepatocellular carcinoma HCC |
| title | The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial |
| title_full | The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial |
| title_fullStr | The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial |
| title_full_unstemmed | The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial |
| title_short | The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial |
| title_sort | efficacy and safety of cadonilimab combined with lenvatinib for first line treatment of advanced hepatocellular carcinoma compassion 08 a phase ib ii single arm clinical trial |
| topic | cadonilimab lenvatinib BsA bi-specific antibody hepatocellular carcinoma HCC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238667/full |
| work_keys_str_mv | AT qianqiao theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT chunhan theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT sisiye theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT juanli theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT guoliangshao theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT yuxianbai theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT aibingxu theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT meilisun theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT weiwang theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT jianwu theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT minghuang theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT lijiesong theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT lukehuang theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT tingliu theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT weiliu theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT zhongminmaxwellwang theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT baiyongli theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT michellexia theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT libai theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT libai theefficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT qianqiao efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT chunhan efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT sisiye efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT juanli efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT guoliangshao efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT yuxianbai efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT aibingxu efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT meilisun efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT weiwang efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT jianwu efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT minghuang efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT lijiesong efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT lukehuang efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT tingliu efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT weiliu efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT zhongminmaxwellwang efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT baiyongli efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT michellexia efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT libai efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial AT libai efficacyandsafetyofcadonilimabcombinedwithlenvatinibforfirstlinetreatmentofadvancedhepatocellularcarcinomacompassion08aphaseibiisinglearmclinicaltrial |