Anti-PD-1 Antibody Alone or in Combination With Decitabine/Chemotherapy in Relapsed or Refractory Malignancies

Anti-PD-1 Antibody Alone or in Combination With Low-dose Decitabine and/or Chemotherapy in Relapsed or Refractory Malignancies: an Open-label Phase I/II Trial

The purpose of this study is to assess the feasibility, safety, and efficacy of anti-PD-1 antibody alone or in combination with low-dose decitabine in patients with relapsed or refractory malignancies, including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.

Study Overview

• Status: Unknown
• Conditions: Malignancies Multiple
• Intervention / Treatment: Drug: Anti-PD-1 antibody; Drug: Decitabine; Drug: Chemotherapy

Detailed Description

Primary objective: To assess the feasibility and safety for Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy administered every 3 weeks to subjects with relapsed or refractory malignancies.

Secondary objectives: 1) To assess the antitumor activity of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy in subjects with relapsed or refractory malignancies. 2) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy. 3) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Exploratory objectives: 1) To analysis of potential biological parameters correlated to clinical response and toxicities. 2) To search predictive biomarkers to guide the choose of patients undergoing the treatment of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Safety Evaluation: Adverse events will be assessed continuously during the study and for 100 days post last treatment, and will be evaluated according to the NCI CTCAE Version 4.0.

Efficacy Evaluation: 1) Treatment response to lymphoma was defined using the International Workshop to Standardize Response Criteria for Lymphomas; 2) Treatment response to solid tumors was defined using Response Evaluation Criteria in Solid Tumors (RECIST1.1).

evaluation index: BOR; ORR; PFS and OS.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Weidong Han, doctor; Phone Number: +86-010-66937463; Email: hanwdrsw@sina.com
• Study Contact Backup: Name: Qingming Yang, doctor; Phone Number: +86-010-55499341; Email: yangqm@medmail.com.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Biotherapeutic Department of Chinese PLA General Hospital
      • Contact: Weidong Han, Doctor; Phone Number: +86-10-66937463; Email: hanwdrsw@sina.com
      • Contact: Qingming Yang, Doctor; Phone Number: +86-10-55499341; Email: yangqm@medmail.com.cn
      • Principal Investigator: Yang Liu, Doctor
      • Principal Investigator: Chunmeng Wang, Master
      • Principal Investigator: Wenying Zhang, Master
      • Principal Investigator: Meixia Chen, Doctor
      • Principal Investigator: Weidong Han, Doctor
      • Principal Investigator: Qingming Yang, Doctor
      • Principal Investigator: Qian Mei, Doctor
      • Principal Investigator: Jing Nie, Doctor
      • Sub-Investigator: Kaichao Feng, Doctor
      • Sub-Investigator: Jingdan Qiu, Doctor
      • Sub-Investigator: Hejin Jia, Doctor
      • Sub-Investigator: Xiang Li, Master
      • Sub-Investigator: Liang Dong, Master
      • Sub-Investigator: Lu Shi, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must have histological confirmation of relapsed or refractory malignancies,including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.
2. 12 to 75 years of age.
3. ECOG performance of less than 2.
4. Life expectancy of at least 3 months.
5. Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria; with solid tumors must have at least one measureable lesion >1 cm per RECIST1.1.
6. Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.

7. Subjects must have adequate bone marrow, live, renal, lung and heart functions.

   1. Absolute neutrophil count greater than or equal to 1,000/μL.
   2. Platelet count greater than or equal to 70,000/µL.
   3. Serum bilirubin level less than or equal to 1.5 x upper limits of normal (ULN).
   4. Serum creatinine less than or equal to 1.5 x ULN.
   5. Alanine aminotransferase [ALT or SGPT] and aspartate aminotransferase [AST or SGOT] less than or equal to 2.5 x ULN.

Exclusion Criteria:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary and intestinal infection especially.
3. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-PD-1 antibody+decitabine; Decitabine will be administrated at 10mg/d on day1 to 5, followed by Anti-PD-1 antibody 200mg on day8 IV Q3 weeks until progression.	Drug: Anti-PD-1 antibody; Anti-PD-1 antibody will be given at 1-3mg/kg on day8 by IV every three weeks; Drug: Decitabine; Decitabine will be given at 10mg/d on day 1to 5 by IV every three weeks
Experimental: Anti-PD-1 antibody; Anti-PD-1 antibody 200mg IV Q3 weeks until progression.	Drug: Anti-PD-1 antibody; Anti-PD-1 antibody will be given at 1-3mg/kg on day8 by IV every three weeks
Experimental: Anti-PD-1 antibody+chemotherapy; Chemotherapy will be given depends on the cancer type and treatment regimen before enrollment. Chemotherapy was administrated on day1 , followed by Anti-PD-1 antibody 200mg on day2 IV Q3 weeks until progression.	Drug: Anti-PD-1 antibody; Anti-PD-1 antibody will be given at 1-3mg/kg on day8 by IV every three weeks; Drug: Chemotherapy; Chemotherapy be given depends on the cancer type and treatment regimen before enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
Progression free survival	3 years
Objective response by Response Evaluation Criteria in Solid Tumors (RECIST1.1).	3 years
Objective response by the International Workshop to Standardize Response Criteria for lymphomas.	3 years

Collaborators and Investigators

• Sponsor: Han weidong
• Investigators: Study Director: Chunmeng Wang, Master, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Study Director: Wenying Zhang, Master, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Study Director: Yang Liu, Doctor, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Study Director: Meixia Chen, Doctor, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Principal Investigator: Yan Zhang, Doctor, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Study Director: Qian Mei, Doctor, Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.; Study Director: Jing Nie, Doctor, Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.; Principal Investigator: Xiang Li, Master, Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.; Principal Investigator: Liang Dong, Master, Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.; Principal Investigator: Lu Shi, Master, Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.; Principal Investigator: Kaichao Feng, Doctor, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Principal Investigator: Jingdan Qiu, Doctor, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853; Principal Investigator: Hejin Jia, Doctor, Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853

Publications and helpful links

General Publications

• Liu Y, Wang C, Li X, Dong L, Yang Q, Chen M, Shi F, Brock M, Liu M, Mei Q, Liu J, Nie J, Han W. Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma. J Immunother Cancer. 2021 Apr;9(4):e002347. doi: 10.1136/jitc-2021-002347.
• Wang C, Liu Y, Dong L, Li X, Yang Q, Brock MV, Mei Q, Liu J, Chen M, Shi F, Liu M, Nie J, Han W. Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy. Clin Cancer Res. 2021 May 15;27(10):2782-2791. doi: 10.1158/1078-0432.CCR-21-0133. Epub 2021 Mar 5.
• Nie J, Wang C, Liu Y, Yang Q, Mei Q, Dong L, Li X, Liu J, Ku W, Zhang Y, Chen M, An X, Shi L, Brock MV, Bai J, Han W. Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2019 Jun 10;37(17):1479-1489. doi: 10.1200/JCO.18.02151. Epub 2019 Apr 30.
• Mei Q, Chen M, Lu X, Li X, Duan F, Wang M, Luo G, Han W. An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma. Oncotarget. 2015 Jun 30;6(18):16698-711. doi: 10.18632/oncotarget.3677.
• Nie J, Zhang Y, Li X, Chen M, Liu C, Han W. DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire. Oncotarget. 2016 Jun 21;7(25):37882-37892. doi: 10.18632/oncotarget.9352.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): May 1, 2019
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 8, 2016
• First Posted (Estimate): November 10, 2016

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: July 5, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: chemotherapy; relapsed or refractory; decitabine; malignancies; anti-PD-1 antibody
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Decitabine; Antibodies
• Other Study ID Numbers: CHN-PLAGH-BT-019