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416 Circularly Permuted TRAIL (CPT) Combined with Thalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study (CPT-MM301)

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Relapsed/Refractory Multiple Myeloma
Hematology Disease Topics & Pathways:
multiple myeloma, Biological, apoptosis, Adult, Diseases, Therapies, Biological Processes, Plasma Cell Disorders, Lymphoid Malignancies, Study Population, Clinically relevant
Sunday, December 6, 2020: 1:00 PM

Wenming Chen, MD1*, Zhongjun Xia, MD, PhD2, Baijun Fang3*, Chengcheng Fu4*, Wei Li, MD5*, Linhua Yang6*, Xiao-yan Ke7*, Hua Jiang, MD8*, Jianyu Weng9*, Li Liu, MD10*, Yaozhong Zhao11*, Xuejun Zhang12*, Aichun Liu, MD13*, Zhongxia Huang14*, Qingzhi Shi15*, Yuhuan Gao16*, Xiequn Chen17*, Ling Pan, MD, PhD18*, Zhen Cai, MD, PhD19*, Zhao Wang, MD20*, Yafei Wang21*, Yaqun Fan22*, Ming Hou23, Yigai Ma24*, Jianda Hu, MD, PhD25, Jianfeng Zhou, MD, PhD26*, Jing Liu, MD, PhD27*, Xiaohong Zhang28*, Haitao Meng, MD, PhD29*, Xuzhang Lu, PhD30*, Bintao Huang31*, Li Fei32, Hanyun Ren, MD33, Zonghong Shao, PhD34, Hebing Zhou35*, Yu Hu, MD36* and Shifang Yang, PhD37

1Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
2Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
3Department of Hematology, Henan Cancer Hospital,Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China
4Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Suzhou, China
5Department of Hematology, The First Hospital of Jilin University, Changchun, China
6Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China
7Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China
8Department of Hematology, Chang Zheng Hospital,Second Military Medical University, Shanghai, China
9Department of Hematology, Guangdong General Hospital,Guangdong Academy of Medical Sciences, Guangzhou, China
10Tangdu Hospital, Air Force Medical University, Xi'an, China
11Department of Lymphoma Center, Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
12Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
13Department of Hematology and Lymphology, Harbin Medical University Cancer Hospital, Harbin, China
14Department of Hematology, Beijing Chao-yang Hospital,Capital Medical University, Beijing, China
15Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
16Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
17Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
18Department of Hematology, West China Hospital,Sichuan University, Chengdu, China
19Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
20Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
21Department of Hematology, Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
22Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Medical College of Xiamen University, Xiamen, China
23Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
24Departmentof Hematology, China-Japan Friendship Hospital, Beijing, China
25Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fuzhou, China
26Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
27Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China
28Department of Hematology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
29Department of Hematology, The First Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, China
30Department of Hematology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
31Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, China
32the First Affiliated Hospital of Nanchang University, Nanchang, China
33Department of Hematology, Peking University First Hospital, Beijing, China
34Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
35Department of Hematology, Beijing Luhe Hospital,Capital Medical University, Beijing, China
36Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
37Beijing Sunbio Biotech Co., Ltd., Beijing, China


CPT, a recombinant permuted human TNF-related apoptosis-inducing ligand (TRAIL), is a first-in-human anti-myeloma drug targeting death receptor 4/5. CPT was found to be a safe and effective anti-myeloma drug as a monotherapy and combined with thalidomide and dexamethasone (TD) in phase 1 and 2 studies for relapsed or refractory multiple myeloma (RRMM) patients. In order to verify the effectiveness and safety of CPT, we have conducted this multi-center, double-blind, placebo-controlled phase 3 study.


In this study, 417 RRMM patients previously treated with two or more lines of therapies were randomly assigned (2:1) to receive CPT+TD (CPT group) vs. placebo+TD (control group) from March 4, 2015 to July 3, 2019 in 36 centers of China.

CPT or placebo at a dose of 10 mg/kg was intravenously administered on days 1 to 5, both groups receive dexamethasone 40 mg orally on days 1 to 4, and thalidomide 150mg daily, 28 days per cycle until to disease progressions or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), overall response rate (ORR), time to progression (TTP), time to response (TTR), duration of response (DOR), health related quality of life (HRQoL) and safety.


Of the 417 patients enrolled, 415 patients received CPT+TD (n=276) or placebo+TD (n=139) treatment. The demographic, baseline disease and clinical characteristic of the two groups were comparable. The median age of the patients was 59 years, and the median time from the initial diagnosis of multiple myeloma (MM) to participating this trial was 2.6 years. The median number of lines of prior therapies was 3. Proteasome inhibitors (PI) and immunomodulators (IMiD) were previously used in 74% and 86.5% of patients, respectively.

At date cutoff, the primary endpoint of PFS was significantly longer in the CPT group than in the control group (median 5.5 vs. 3.1 months; hazard ratio [HR] 0.619; P<0.0001) (Figure). The key secondary endpoints, including ORR (30.4% vs. 13.7%, P=0.0002) and OS (median 21.8 vs.17.0 months; HR, 0.723; P=0.0166) were also significantly improved in the CPT group than in the control group (Figure). Subgroup analysis of PFS, OS and ORR showed the superiority of CPT+TD over placebo +TD in almost all subgroups (Figure). It is particularly interesting to note that CPT exhibited excellent efficacy consistently with PFS, OS and ORR in the subgroups of patients with a poor prognosis, including those with refractory MM, with previous PI and IMiD therapies, and those received >3 lines of prior therapies. PFS and ORR were also significantly improved in the patients with PI and IMiD double-refractory MM. The other secondary endpoints including TTP, DOR and HRQoL also showed the superiority of the CPT group over the control group. To date of cutoff, the events of disease progressions or death occurred in 203 patients (73.6%) in the CPT group vs.111 patients (79.9%) in the control group.

The serious adverse events (SAE) rates were similar in the CPT group and the control group (40.6% vs. 37.4%), as were the death rates during the treatments (7.6% vs. 8.6%). Treatment-emergent adverse events (TEAEs) with at least a 10% greater frequency in the CPT group vs. the control group were elevated alanine transaminase (ALT), elevated aspartate transaminase (AST), elevated lactate dehydrogenase (LDH), increased monocyte counts, hypocalcaemia and upper respiratory tract infections. The data suggested that CPT may induce hepatotoxicity in patients, most of which were grade 1 or 2 and reversible. Grade 3 or 4 TEAEs observed in the CPT group and the control group included decreased neutrophil counts (26.8% vs. 26.6%), pneumonia (25% vs. 23.7%) and hyperglycemia (21% vs. 12.2%).


This study demonstrated that CPT was an effective drug for the treatment of RRMM patients, even in the multi-line treated MM patients and PI and/or IMIDs refractory MM patients. The combination of CPT with TD significantly prolonged the PFS and OS, increased the ORR. CPT combined with TD was well tolerated, the adverse events were mild, transient and reversible. CPT is expected to be the first available anti-myeloma drug that targets death receptor 4/5.

Disclosures: Yang: Beijing Sunbio Biotech Co., Ltd: Current Employment.

*signifies non-member of ASH